Pure standard detooxification in methanol was used to Carcinogen detoxification methods a standard curve. and Qiu,S. Even if you lose body weight, the fat in your liver will stay.

Carcinogen detoxification methods -

But are our bodies really full of toxins? And do we need help to get rid of them? The most important thing you can do to help your body rid itself of toxins is take care of your liver.

Fact: If you overindulge too often, that can damage the liver over time. Fried foods and sugary drinks are difficult for the liver to process, and too much of each of these things become fat in the liver. Even if you lose body weight, the fat in your liver will stay. This is what is known as non-alcoholic fatty liver disease.

And if you switch to a healthy, plant-based diet of lean proteins, whole grains, fruits and vegetables, you will likely get all the benefits detox products claim to offer. This includes reduced inflammation , improved digestion, more energy and a boost to your immune system.

Some call for complete fasting, water or juice-only fasting, strict diets of only fruits and vegetables, or use of herbs, teas, supplements or enemas. Strict regimens like these can cause electrolyte imbalances, vitamin and mineral deficiencies, diarrhea and other stomach problems, and fatigue.

These two things raise a red flag for safety. And keep in mind, herbal detoxes or supplements do not have to be reviewed for safety and effectiveness by the Food and Drug Administration before being sold. If you think you may be deficient in a specific nutrient , talk to your doctor to figure out if you need anything extra.

A detox can have a big impact on your body, but not necessarily in the way you hope for. So, if you are considering a detox or weight loss plan, make sure you talk to your doctor first.

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Cancerwise 10 4 detox myths: Get the facts. Jump To:. The Mahidol University Central Institutional Review Board provided ethics approval for this study project No. All participants signed the informed written consent before this study. This study was registered at the Thai Clinical Trial Registry with No.

This project was a pre-post clinical trial performed with healthy, regular smokers. They were able to consume Nutri-PEITC jelly; avoid eating cruciferous vegetables such as watercress, kale, cabbage, broccoli, Chinese cabbage, cauliflower, radishes, mustard, and wasabi; and avoid drinking alcoholic beverages for at least 24 h before enrolling in the study and throughout the study period.

The exclusion criteria were as follows: having cancer or a history of cancer, liver, or kidney diseases; and taking paracetamol, chlorzoxazone, or N -acetylcysteine within 24 h before participating in the study and throughout the study period.

Paracetamol and chlorosazone have the same metabolism as PEITC, 14 while N -acetylcysteine can conjugate to PEITC. The researcher calculated the sample size based on data from a previous study by Hecht et al. Based on the mean difference of NNAL in the urine of 0.

Using the G-power program with the principle of noncentrality parameter, the sample size for a paired t-test with an alpha value of 0. The Nutri-PEITC jelly product was obtained from the Dental Innovation Foundation under Royal Patronage.

It is a semi-solid nutritious food gel Fig. Each cup contains 10 mg of PEITC and provides an energy of kcal. The jelly was produced by using ultra-high temperature processing and aseptic filling into sterile cups at a Good Manufacturing Practices-certified plant.

The participants were asked to consume four cups of Nutri-PEITC jelly per day to achieve a dose of 40 mg of PEITC per day. They were instructed to consume Nutri-PEITC jelly about 1. Louis, MO, USA , NNN, pyridine-ring-deuterated N -nitrosonornicotine NNN-d 4 , NNAL, and methyl-deuterated 4- methylnitrosamino 3-pyridyl butanol NNAL-d 3 were purchased from Toronto Research Chemicals, Ontario, Canada.

Oasis MCX 1 cc Vac cartridges 30 mg of sorbent per cartridge, 30 µm were obtained from Waters GmbH, Darmstadt, Germany. Positive displacement pipette Rainin, Mettler-Toledo S.

This study was conducted at the Institute of Nutrition, Mahidol University. Thirty participants joined this project for seven days, divided into two periods, i. For the pre-intervention period, each participant was asked to smoke regularly and to collect their hour urine into three containers per day 1 L per container.

Each container was prefilled with 5 mL of ammonium sulfamate preservative mg in 5 mL of 1 N sulfuric acid. At the end of three days, the participants returned the urine-filled containers. Then, for the postintervention period, the participants were instructed to smoke regularly, consume four cups of Nutri-PEITC jelly per day for three consecutive days, and collect their hour urine in a similar way as during the pre-intervention period.

The urine samples of each day were randomly sampled into a milliliter tube. Throughout the study, all participants recorded all meals, the brand of cigarettes smoked, the number of cigarettes smoked, the number of consumed Nutri-PEITC jelly products, and adverse events if any.

To ensure the consistency of smoking throughout the study, the levels of cotinine in the urine during the pre-intervention and postintervention periods were compared. Cotinine was measured by a cotinine enzyme-linked immunosorbent assay kit Cat.

KA, Abnova, Taiwan , as described previously. Then, µL of the enzyme conjugate was added to each well.

The plate was shaken for 10—30 s with a microplate shaker Fisher Scientific, Waltham, MA, USA to ensure proper mixing. After incubating at room temperature 20—25 °C in the dark for 60 min, the wells were washed three times with µL of 1× washing buffer.

Then, all liquid was aspirated with a multichannel pipette 8-channel pipettor, Axygen, Corning, NY, USA. To ensure that all residual moisture was removed, the plate was then inverted and vigorously slapped on an absorbent paper.

This step is critical to ensure that the residual enzyme conjugate does not skew the results. After the plate was dried, µL of substrate reagent was added to each well. The plate was incubated at room temperature in the dark for 30 min. Then, µL of stop solution was added to each well, and the plate was shaken gently to mix the solution.

The absorbance at nm was read by using a plate reader Epoch model, BioTek, Agilent, Santa Clara, CA, USA within 15 min after addition of the stop solution. After centrifugation at 25 °C and 1, g for 3 min, µL of each of the top hexane layers containing PEITC was collected into a two-milliliter tube for all samples.

Hexane extraction was performed once more, and the supernatant was combined with the first extract. Then, ammonia derivatization was performed by adding µL of 2 M ammonia in methanol into the hexane extract.

The samples were vortexed for 30 s and incubated on a microplate shaker Fisher Scientific, USA at room temperature for 4 h. Next, the samples were dried with a speed vacuum evaporator CentriVap Benchtop Vacuum Concentrator, Labconco, Kansas City, MO, USA at 55 °C for 40 min to remove the solvents.

Then, all samples were filtered through a nylon filter 0. Positive ion electrospray ionization was used for mass spectrometric analysis with a spray voltage of 3, V, sheath gas of 50 arbitrary units, and auxiliary gas of The ion transfer tube and vaporizing temperatures were °C and °C, respectively.

The retention time of phenethyl thiourea was 1. A collision energy of The primary outcome measures were total NNN and total NNAL metabolites in the urine.

The urine samples were prepared according to a previous study. In brief, the stored urine samples from the pre- or postintervention periods of three days were pooled into one milliliter tube. As shown in Figure S1 , 6 mL of urine was treated with 40 µL of β-glucuronidase in phosphate buffer pH 7.

This procedure freed the Gluc-conjugated metabolites, allowing the determination of total metabolites including conjugated and unconjugated forms. Ten microliters of the eluate dissolved in 0. Chromatography was performed on a Hypersil gold C18 column × 2.

The mobile phase solvents included 15 mM ammonium acetate A and 0. The mobile phase solvents were run with a flow rate of 0. The quantitative and confirmative fragment ions of the internal standard NNN-d 4 were The precursor masses of NNAL and the internal standard NNAL-d 3 were and , respectively.

The quantitative fragment ion of NNAL-d 3 was Pure standard dissolved in methanol was used to generate a standard curve. The standard curve for the quantitation of NNN was generated between the concentration of NNN and the ratios between the area under the curve of NNN and the internal standard NNN-d 4.

Likewise, the standard curve for the quantitation of NNAL was created between the concentration of NNAL and the ratios between the area under the curve of NNAL and the internal standard NNAL-d 3. The standard concentrations of NNN included 1.

While the standard concentrations of NNAL included 0. For the baseline characteristics of the participants, numerical data were presented as the mean ± standard deviation and categorical data were expressed as the number of participants. Then, the number of metabolites in µL of the sample was obtained, followed by the calculation based on the fact that µL of the sample came from 6 mL of urine.

In addition, the urine sample of each person had a different content of water. Therefore, the weight of urine creatinine was used to adjust for the variation and yielded the level of metabolites per gram of creatinine. The level of urinary metabolites was compared between the pre-and postintervention periods by using the Wilcoxon matched-pairs signed-rank test due to a skewed distribution.

All statistical tests were performed by using a two-tailed test. Graph Pad Prism V. Power analysis was performed by using G-power V.

As shown in Figure 2 , 49 participants were recruited. After the screening, 17 participants were excluded; 11 participants had high liver enzymes and six participants were unable to be followed up. Thirty-two participants received the intervention. One participant withdrew from the study due to suffering from the lack of vegetable consumption.

One participant was excluded after the analysis due to highly deviated data. Finally, data from 30 participants were included in the analysis. Table 1 shows that the average age of the participants was The average amount of smoking was The majority of participants rarely consumed vegetables only once a month.

Table 3 shows that most of the participants consumed the required amount of jelly and were able to avoid consuming cruciferous vegetables throughout the study.

Table 4 shows the number of participants refraining from vegetable consumption completely or still consuming a small amount of vegetables less than 50 g per day , as specified. The table shows the number of participants consuming Nutri-PEITC jelly as specified. As shown in Figure 3a , there were no significant differences in the number of cigarettes smoked between the pre- and postintervention periods.

Consistently, Figure 3b shows no significant difference in the average urinary cotinine levels between the pre- and postintervention periods. P -values were obtained from Wilcoxon signed-rank tests.

The line plot c shows the standard curve between the concentrations of standard PEITC and the area under the curves of phenethyl thiourea determined by liquid chromatography-tandem mass spectrometry. The R 2 and p -values were obtained by linear regression analysis.

As shown in Table 5 , nonserious adverse events, including nausea, dry mouth, and diarrhea, occurred on the first day of Nutri-PEITC jelly intake and disappeared without treatment. All participants were able to tolerate these minor events from Nutri-jelly intake.

Figures 4a, b and 5a, b show chromatograms of NNN and the internal standards, respectively, and the standard curve. Figure 6a, b shows chromatograms of NNAL and the internal standards, respectively, and the standard curve.

As shown in Figure 6c , the average level of total urinary NNN metabolites normalized with the creatinine level during the postintervention period after consuming Nutri-PEITC jelly was greater than that of the pre-intervention period before consuming the jelly.

Due to the large individual variation, the difference was not statistically significant. Liquid chromatography-tandem mass spectrometry chromatograms of NNN a and the internal standard, NNN-d 4 b. The left panel shows a liquid chromatography chromatogram with the specified retention time RT.

The right panel shows the mass spectrometry chromatograms of the quantitative top panel with orange filled and confirmative lower panel without filling fragment masses. The standard curves of NNN a and NNAL b show the mean ± standard deviation of triplicate ratios of the area under the curve between standard NNN and the internal standard IS pyridine-ring-deuterated NNN a or standard NNAL and the IS methyl-deuterated NNAL b at each concentration.

The R 2 and p -values were obtained from linear regression analysis. Liquid chromatography-tandem mass spectrometry chromatograms of NNAL a and the internal standard, NNAL-d 3 b. Previous human studies have suggested that PEITC can help to detoxify the smoking-derived carcinogen NNK. Similarly, previous animal studies have indicated that PEITC can help to detoxify the tobacco-specific oral carcinogen NNN.

In this study, we found that consuming Nutri-PEITC jelly significantly increased the total urinary NNN metabolites, with no significant change in the total urinary NNAL metabolites. The major form of NNN metabolites in urine is the nontoxic NNN- N -Gluc, which is formed by the phase II enzyme UDP glucuronyltransferase.

Previous studies also have shown that an achievable dose of PEITC in humans can activate UDP glucuronyltransferase. Since NNN is known to induce oral carcinogenesis, 4 Nutri-PEITC jelly may be a good candidate for the primary prevention of oral cancer in active smokers.

Owing to its better absorption in the form of the Nutri-Jelly matrix than in oil, 13 future randomized controlled trials are warranted to study the effect of Nutri-PEITC jelly, compared with that of PEITC in oil, on biomarkers of oral carcinogenesis. In , Hecht et al.

reported that the consumption of watercress These seemingly contradictory results may be explained by the complex effect of PEITC on both phase I and II enzymes. Since PEITC can both inhibit phase I enzymes and stimulate phase II enzymes, 25 treatment with PEITC likely reduces the formation of NNAL but promotes the formation of NNAL-Gluc, resulting in no changes of the total NNAL metabolites, as observed in this study.

In , Yuan et al. The strengths of this research included multiple days of urine collection. The result of urinary metabolites in each participant came from the averaged pool sample of three days.

Furthermore, the smoking habits were followed up throughout the study. The results showed that all participants smoked the same type and number of cigarettes throughout the trial period, supported by the constant urinary cotinine levels.

In addition, this work was performed in healthy smokers, so the results may have application in primary cancer chemoprevention. Furthermore, all participants were asked to refrain from cruciferous vegetables throughout the study. Therefore, their baseline levels of urinary PEITC in the pre-intervention period were very low, allowing us to see a significant increase in the PEITC levels after consuming the Nutri-PEITC jelly.

Nevertheless, there were some limitations to this study. First, it was a nonrandomized pre-post study. Therefore, some potential biases still may have occurred.

In the future, a randomized controlled trial should be conducted to compare the effect of Nutri-PEITC jelly with that of Nutri-jelly as a placebo control to investigate its long-term effects on carcinogen detoxification and DNA adducts. Also, comparative studies for the effect of Nutri-PEITC on heavy and moderate smokers as well as long-term vs.

recent smoker groups are warranted. Second, in this study, we did not directly measure the changes in phase I and II enzyme activities after Nutri-PEITC intake. Since the metabolism occurs mostly in the liver, it is challenging to measure the enzyme activities in humans.

Thus, we discussed the possible mechanism of PEITC based on previous in-vitro and in-vivo studies. In addition, human liver microsomes may be used as a tool for further investigations of the molecular mechanism. Third, the response to PEITC in jelly may also be dependent on other factors, such as the efficacy of liver enzymes and polymorphisms of the GST gene, which affect the metabolism of PEITC.

Furthermore, a recent review suggests that local exposure to bioactive compounds can provide effective chemoprevention. This pre-post clinical trial of Nutri-jelly PEITC in smokers demonstrated that Nutri-PEITC jelly significantly increased the total urinary NNN, with no significant change in the total urinary NNAL.

NNN-Gluc is the major form of urine metabolites. Therefore, these findings suggest that Nutri-PEITC jelly may increase the detoxification of smoking-derived carcinogens by promoting Gluc conjugation of NNN, the tobacco-specific oral carcinogen.

To confirm its potential for the primary prevention of smoking-related oral cancer, future randomized controlled trials are warranted to study the effect of Nutri-PEITC jelly, compared with that of PEITC in oil, on biomarkers of oral carcinogenesis.

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Carcinogen detoxification methods -

As shown in Figure 2 , 49 participants were recruited. After the screening, 17 participants were excluded; 11 participants had high liver enzymes and six participants were unable to be followed up.

Thirty-two participants received the intervention. One participant withdrew from the study due to suffering from the lack of vegetable consumption. One participant was excluded after the analysis due to highly deviated data. Finally, data from 30 participants were included in the analysis.

Table 1 shows that the average age of the participants was The average amount of smoking was The majority of participants rarely consumed vegetables only once a month. Table 3 shows that most of the participants consumed the required amount of jelly and were able to avoid consuming cruciferous vegetables throughout the study.

Table 4 shows the number of participants refraining from vegetable consumption completely or still consuming a small amount of vegetables less than 50 g per day , as specified.

The table shows the number of participants consuming Nutri-PEITC jelly as specified. As shown in Figure 3a , there were no significant differences in the number of cigarettes smoked between the pre- and postintervention periods. Consistently, Figure 3b shows no significant difference in the average urinary cotinine levels between the pre- and postintervention periods.

P -values were obtained from Wilcoxon signed-rank tests. The line plot c shows the standard curve between the concentrations of standard PEITC and the area under the curves of phenethyl thiourea determined by liquid chromatography-tandem mass spectrometry.

The R 2 and p -values were obtained by linear regression analysis. As shown in Table 5 , nonserious adverse events, including nausea, dry mouth, and diarrhea, occurred on the first day of Nutri-PEITC jelly intake and disappeared without treatment. All participants were able to tolerate these minor events from Nutri-jelly intake.

Figures 4a, b and 5a, b show chromatograms of NNN and the internal standards, respectively, and the standard curve.

Figure 6a, b shows chromatograms of NNAL and the internal standards, respectively, and the standard curve. As shown in Figure 6c , the average level of total urinary NNN metabolites normalized with the creatinine level during the postintervention period after consuming Nutri-PEITC jelly was greater than that of the pre-intervention period before consuming the jelly.

Due to the large individual variation, the difference was not statistically significant. Liquid chromatography-tandem mass spectrometry chromatograms of NNN a and the internal standard, NNN-d 4 b. The left panel shows a liquid chromatography chromatogram with the specified retention time RT. The right panel shows the mass spectrometry chromatograms of the quantitative top panel with orange filled and confirmative lower panel without filling fragment masses.

The standard curves of NNN a and NNAL b show the mean ± standard deviation of triplicate ratios of the area under the curve between standard NNN and the internal standard IS pyridine-ring-deuterated NNN a or standard NNAL and the IS methyl-deuterated NNAL b at each concentration.

The R 2 and p -values were obtained from linear regression analysis. Liquid chromatography-tandem mass spectrometry chromatograms of NNAL a and the internal standard, NNAL-d 3 b. Previous human studies have suggested that PEITC can help to detoxify the smoking-derived carcinogen NNK.

Similarly, previous animal studies have indicated that PEITC can help to detoxify the tobacco-specific oral carcinogen NNN. In this study, we found that consuming Nutri-PEITC jelly significantly increased the total urinary NNN metabolites, with no significant change in the total urinary NNAL metabolites.

The major form of NNN metabolites in urine is the nontoxic NNN- N -Gluc, which is formed by the phase II enzyme UDP glucuronyltransferase. Previous studies also have shown that an achievable dose of PEITC in humans can activate UDP glucuronyltransferase.

Since NNN is known to induce oral carcinogenesis, 4 Nutri-PEITC jelly may be a good candidate for the primary prevention of oral cancer in active smokers. Owing to its better absorption in the form of the Nutri-Jelly matrix than in oil, 13 future randomized controlled trials are warranted to study the effect of Nutri-PEITC jelly, compared with that of PEITC in oil, on biomarkers of oral carcinogenesis.

In , Hecht et al. reported that the consumption of watercress These seemingly contradictory results may be explained by the complex effect of PEITC on both phase I and II enzymes. Since PEITC can both inhibit phase I enzymes and stimulate phase II enzymes, 25 treatment with PEITC likely reduces the formation of NNAL but promotes the formation of NNAL-Gluc, resulting in no changes of the total NNAL metabolites, as observed in this study.

In , Yuan et al. The strengths of this research included multiple days of urine collection. The result of urinary metabolites in each participant came from the averaged pool sample of three days.

Furthermore, the smoking habits were followed up throughout the study. The results showed that all participants smoked the same type and number of cigarettes throughout the trial period, supported by the constant urinary cotinine levels.

In addition, this work was performed in healthy smokers, so the results may have application in primary cancer chemoprevention. Furthermore, all participants were asked to refrain from cruciferous vegetables throughout the study. Therefore, their baseline levels of urinary PEITC in the pre-intervention period were very low, allowing us to see a significant increase in the PEITC levels after consuming the Nutri-PEITC jelly.

Nevertheless, there were some limitations to this study. First, it was a nonrandomized pre-post study. Therefore, some potential biases still may have occurred. In the future, a randomized controlled trial should be conducted to compare the effect of Nutri-PEITC jelly with that of Nutri-jelly as a placebo control to investigate its long-term effects on carcinogen detoxification and DNA adducts.

Also, comparative studies for the effect of Nutri-PEITC on heavy and moderate smokers as well as long-term vs. recent smoker groups are warranted.

Second, in this study, we did not directly measure the changes in phase I and II enzyme activities after Nutri-PEITC intake. Since the metabolism occurs mostly in the liver, it is challenging to measure the enzyme activities in humans.

Thus, we discussed the possible mechanism of PEITC based on previous in-vitro and in-vivo studies. In addition, human liver microsomes may be used as a tool for further investigations of the molecular mechanism. Third, the response to PEITC in jelly may also be dependent on other factors, such as the efficacy of liver enzymes and polymorphisms of the GST gene, which affect the metabolism of PEITC.

Furthermore, a recent review suggests that local exposure to bioactive compounds can provide effective chemoprevention. This pre-post clinical trial of Nutri-jelly PEITC in smokers demonstrated that Nutri-PEITC jelly significantly increased the total urinary NNN, with no significant change in the total urinary NNAL.

NNN-Gluc is the major form of urine metabolites. Therefore, these findings suggest that Nutri-PEITC jelly may increase the detoxification of smoking-derived carcinogens by promoting Gluc conjugation of NNN, the tobacco-specific oral carcinogen. To confirm its potential for the primary prevention of smoking-related oral cancer, future randomized controlled trials are warranted to study the effect of Nutri-PEITC jelly, compared with that of PEITC in oil, on biomarkers of oral carcinogenesis.

The authors thank Ms. Ketsara Phadungrerk for her support in subject recruitment and data collection. Mahidol University Central Institutional Review Board MU-CIRB provided ethical approval with project No.

The study was conducted according to the Declaration of Helsinki and the International Conference on Harmonization Guidelines for Good Clinical Practice ICH-GCP. All participants signed the informed written consent before the study. This study was supported by the Dental Innovation Foundation under Royal Patronage AOF3 , Thailand.

DT and AL received a grant and the Nutri-jelly product for the trial from the nonprofit organization Dental Innovation Foundation under Royal Patronage, Thailand. However, the funder was not involved in the research design or operation.

One of the authors, Prof. Dunyaporn Trachootham, has been an editorial board member of Cancer Screening and Prevention since July The authors have full control of the reported data.

The other authors have no conflicts of interest. NP designed the study, performed the clinical trial and laboratory analysis, analyzed the data, and drafted the manuscript. PT and AL designed the study and provided scientific input for discussion.

DT obtained the grant, pursued ethics approval, designed the study, supervised the clinical trial and laboratory analysis, and edited the manuscript.

All authors approved the final version of the submitted manuscript. Phikulkhao N, Tanaviyutpakdee P, Lam-ubol A, Trachootham D. Nutri-phenethyl Isothiocyanate Jelly Promotes Detoxification of a Tobacco-specific Oral Carcinogen in Male Active Cigarette Smokers.

Cancer Screening and Prevention. Journal of Clinical and Translational Hepatology Exploratory Research and Hypothesis in Medicine Journal of Exploratory Research in Pharmacology Journal of Clinical and Translational Pathology Cancer Screening and Prevention Future Integrative Medicine Gene Expression Journal of Translational Gastroenterology Oncology Advances Chronic Metabolic Diseases.

Author information. Cancer Screening and Prevention ; 2 1 : 30 - Abstract Background and objectives Phenethyl isothiocyanate PEITC , a phytochemical from cruciferous vegetables, is known to modulate detoxification enzymes.

Methods This pre-post trial was conducted on 30 healthy, male, regular smokers. Conclusions The findings suggest that intake of Nutri-PEITC jelly may increase the detoxification of NNN, a tobacco-specific oral carcinogen, likely by promoting glucuronide conjugation.

Keywords PEITC, Brassica vegetable, Functional food, Carcinogen, Active Smoking, Metabolites, Clinical trial, Primary Cancer Prevention. Introduction Smoking is the top risk factor in many types of cancer, especially lung and oral cancer. Materials and methods Ethical aspects and setting The Mahidol University Central Institutional Review Board provided ethics approval for this study project No.

Intervention The Nutri-PEITC jelly product was obtained from the Dental Innovation Foundation under Royal Patronage. Characteristic Range Mean Standard deviation Age years 19—50 Table 3 Compliance of Nutri-PEITC jelly intake. Table 4 Monitoring of vegetable consumption before and after Nutri-PEITC intake.

Day Pre-intervention period Postintervention period 1 st day 2 nd day 3 rd day 4 th day 5 th day 6 th day Refrain completely 28 29 29 30 29 29 Consumed Cabbage 0 0 1 0 1 1 Cantonese lettuce 1 0 0 0 0 0 Chinese kale 1 1 0 0 0 0.

The table shows the number of participants with specified conditions. Table 5 Adverse events reported after intake of Nutri-PEITC jelly. N -nitrosonornicotine NNN and pyridine-ring-deuterated N -nitrosonornicotine NNN-d 4. N -nitrosonornicotine NNN and 4- methylnitrosamino 3-pyridyl butanol NNAL metabolites in the urine after consuming Nutri-phenethyl isothiocyanate jelly.

S1 Sample preparation for determination of urinary NNN and NNAL metabolites. DOCX Click here for additional data file. Table S1 Conditions of mass spectrometric analysis. References 1 El-Bayoumy K, Christensen ND, Hu J, Viscidi R, Stairs DB, Walter V, et al.

An Integrated Approach for Preventing Oral Cavity and Oropharyngeal Cancers: Two Etiologies with Distinct and Shared Mechanisms of Carcinogenesis.

Tobacco carcinogens, their biomarkers and tobacco-induced cancer. Tobacco-specific nitrosamines and their pyridine-N-glucuronides in the urine of smokers and smokeless tobacco users. Human urinary carcinogen metabolites: biomarkers for investigating tobacco and cancer. Proof of Concept of a Personalized Genetic Risk Tool to Promote Smoking Cessation: High Acceptability and Reduced Cigarette Smoking.

Updated May 24 Isothiocyanates and Xenobiotic Detoxification. Clinical Trial of 2-Phenethyl Isothiocyanate as an Inhibitor of Metabolic Activation of a Tobacco-Specific Lung Carcinogen in Cigarette Smokers.

Effects of watercress consumption on metabolism of a tobacco-specific lung carcinogen in smokers. Nutri-jelly may improve quality of life and decrease tube feeding demand in head and neck cancer patients. Pharmacokinetic, safety, and tolerability studies after single and multiple oral administration of Phenethyl isothiocyanate in Nutri Jelly.

The mercapturic acid pathway. A cautionary note on using N-acetylcysteine as an antagonist to assess isothiocyanate-induced reactive oxygen species-mediated apoptosis. The inhibition of cytochrome P 2Acatalyzed NNK metabolism by NAT, NAB and nicotine.

Urinary cotinine as a biomarker of cigarette smoke exposure: a method to differentiate among active, second-hand, and non-smoker circumstances. Determination of phenethyl isothiocyanate in human plasma and urine by ammonia derivatization and liquid chromatography-tandem mass spectrometry.

Detoxification of heterocyclic aromatic amines from grilled meat using a PEITC-rich vegetable sauce: a randomized crossover controlled trial. Normalisation of urinary biomarkers to creatinine for clinical practice and research—when and why.

Effect of phenethyl isothiocyanate on the metabolism of tobacco-specific nitrosamines by cultured rat oral tissue. Effects of phenethyl isothiocyanate, a carcinogenesis inhibitor, on xenobiotic-metabolizing enzymes and nitrosamine metabolism in rats.

Induction of epoxide hydrolase, glucuronosyl transferase, and sulfotransferase by phenethyl isothiocyanate in male Wistar albino rats. Isothiocyanates induce UGT1A1 in humanized UGT1 mice in a CAR dependent fashion that is highly dependent upon oxidative stress.

Analysis of N- and O-glucuronides of 4- methylnitrosamino 3-pyridyl butanol NNAL in human urine. Chapter Three - Cytoprotective Role of Dietary Phytochemicals against Cancer Development via Induction of Phase II and Antioxidant Enzymes.

Dosage Forms. Resveratrol modulates drug- and carcinogen-metabolizing enzymes in a healthy volunteer study. PEITC: Functional Compound for Primary and Tertiary Chemoprevention of Cancer.

A Way Forward for Cancer Chemoprevention: Think Local. Copyright © Authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 4.

Cancer Screening and Prevention pISSN eISSN Article Options PDF views Full Article views Highlights COI Form Checklist. Cite this Article Phikulkhao N, Tanaviyutpakdee P, Lam-ubol A, Trachootham D. Copied to clipboard Copy Export to RIS Export to EndNote.

This mechanism, with hydride migration, is generally viewed as a part of the oxidation of terminal olefins with an aldehyde product 39 , Reactive haloacyl halides are produced 41 ; the relevance of these and the epoxides themselves to genotoxicity remains to be established. In Rannug reported the GSH-dependent activation of 1,2-dichloroethane This pathway is now well-established, with an episulfonium ion intermediate 42 and several characterized DNA adducts The general pathway has been extended to dihalomethanes, although very limited information is available about DNA adducts The same pathway appears to apply to trihalomethanes Although many of the basic methods existed in , the past two decades have seen an explosion of capability in two major areas.

The first area involves chromatography and spectroscopy. HPLC has been developed as a necessary technique in the area. Capillary electrophoresis and other new separation techniques have potential. NMR and mass spectrometry were already very important in but today both methods have much greater resolution and sensitivity and are coupled on-line with HPLC.

Other spectroscopic methods such as fluorescence 46 have been applied to DNA adduct studies. These approaches were in their infancy in In the first P cDNA sequence was published 48 , and the characterization of the enzymes involved in carcinogen metabolism would have been impossible without these methods.

Scarce proteins can be identified, characterized, and produced in large amounts. As an aside, it should be emphasized that human tissue samples are now much more readily available than in and have been invaluable in extending work from animal models to humans. By many of the general concepts about the significance of enzymes in carcinogen metabolism had been developed, at least in principle.

For instance, enzymes such as P were known to be inducible 49 , enzymatic differences could be used to explain variable susceptibility of individual animals to carcinogens 50 , and some evidence for P polymorphism as a risk factor in lung cancer had been presented Enzymology had been used successfully to address issues regarding the existence of multiple enzyme forms within some multi-gene families 52 — Protein chemistry and, later, molecular biology techniques were developed to characterize the enzymes involved in carcinogen metabolism, both in terms of the enzymology and also regulation of gene expression.

This work was done with experimental animal models and, most importantly, with humans. Today there is a reasonably good understanding of many individual enzymes e. individual Ps, GSH transferases, etc.

in terms of their concentrations in various human tissues, the extent of variability among humans, and the involvement of these enzymes in particular steps in metabolism of chemical carcinogens The approaches are used rather routinely and many have been relatively straightforward, although the overall significance of a particular reaction to tumorigenesis may not always be clear.

Inter-individual variation in the enzymes involved in carcinogen metabolism is now extensively studied. To date there has been impressive success in the application of information about human Ps in the development of new drugs in the pharmaceutical industry There is optimism that such approaches will also be productive in the prediction of cancer risks due to inter-individual variations in enzymes.

The National Institute of Environmental Health Sciences has begun an Environmental Genome Project, in which the long-term goal is to associate risks with polymorphisms of the genes involved in carcinogen metabolism, as well as others The overall appreciation, characterization and organization of information about individual genes has developed dramatically since Chemoprevention is discussed in another article in this issue Also of interest, however, are reports that some of the chemopreventive agents can increase the toxicity, or at least DNA adduct formation, by inducing the conjugating enzymes 67 , The majority of the major systems used today was done before During the past decade many improvements in the systems have been made, particularly in terms of integration with enzyme systems of mammalian origin.

Purified enzymes and human microsomes have been added to Salmonella typhimurium -based systems, both in the classic Ames' reversion assay 69 and an SOS response-based colorimetric assay 70 , in order to define roles of individual enzymes. Another approach is to express individual enzymes, or sets of enzymes, and reporter genes within cells.

Such approaches have been utilized with mammalian cells 71 and bacteria Both S. typhimurium and Escherichia coli -based systems with Ps have been used 73 — One of the problems with in vitro results obtained in some of the systems described above is that the relevance of metabolism in different tissues may be difficult to relate to in vivo problems, e.

One approach is the use of PBPK models, which have been developed mainly in the past 20 years. A common strategy is to: i define specific enzymatic steps of major relevance to bioactivation and detoxification; ii identify the most important tissues, in terms of metabolism and as targets for tumor development; iii collect data on rates of all relevant enzymatic transformations in vitro , with tissues of interest both from humans and experiment models; iv if possible i.

with reasonably weak cancer suspects such as industrial solvents , validate the model in humans with low exposures; and v on the basis of comparisons and predictions about the effective concentration of the activated carcinogen delivered at the target site in humans and animals, compare the risk of concentrations of the chemical to humans to those known to produce tumors in the experimental animal models 76 , This strategy has been used with information about lung and liver measurements of CH 2 Cl 2 metabolism by P 2E1 and GSH transferase T1 78 , and as a consequence the Environmental Protection Agency revised its exposure limit upwards.

Although much progress has been made in the past 20 years and the field has matured, there are a number of remaining challenges that must be considered. These involve the general significance of the field and the basis for development of related areas, such as genomics.

Despite all of the knowledge of pathways obtained in the past half-century or more 79 , the reactions remain to be established in many cases. Some notable examples include the GSH conjugation of trihalomethanes found in drinking water 45 and the oxidation products of trichloroethylene, at least those that are involved in reactions with macromolecules 9 [a separate issue is the contribution of an alternate, GSH-dependent pathway to activation 80 , 81 ].

Another issue involves the chemical characterization of the DNA adducts generated by oxidations of several compounds by peroxidases e. myeloperoxidase, cyclooxygenase, etc.

Understanding mechanistic details of one transformation is critical in making predictions about others. Much remains to be understood about most of the enzymes under consideration here for recent review on the enzymes of interest, see ref. The questions relate to both structure and catalysis which are not unrelated.

With some of the enzymes, the availability of crystal structures has facilitated progress 87 , 88 ; more are needed. Enzymology issues with practical implications include the question of whether Ps can catalyze 1-electron oxidation of polycyclic aromatic hydrocarbons This hypothesis seems reasonable but has been difficult to address The meaning of K m in most of the enzymatic transformations is not well understood 90 — 92 ; what does this value mean when incorporated into PBPK models 93?

Genomics is a popular field today, and in the area of carcinogen metabolism there is much anticipation that genetic differences in the enzymes of interest will be associated with major differences in cancer risk. Two major issues must be addressed in the course of a massive study.

The first is the identification of the major allelic variants of the genes that code for the enzymes under consideration. This effort will require large-scale sequencing efforts. In some enzyme families not all of the individual genes have been identified yet 94 , The second issue is functional analysis.

One approach to assessing the significance of genetic variations is to go directly to epidemiological correlations. However, the danger of going directly to such associations in the absence of basic scientific information has been demonstrated in the work with P 2D6 96 , A logical approach is development of functional analysis systems, in which allelic variants of enzymes can be expressed and examined for parameters relevant to metabolism of relevant carcinogens.

For further discussion of the complexity and relevant issues, see ref. In a sense, most of the progress made in the regulation of the enzymes of interest has been made in the past 20 years, primarily because of the development of useful methodology.

Today, much is known about the systems, but even more questions remain. In many cases, even the primary responsive elements receptors remain to be identified and fully characterized [e.

antioxidant response element system 98 — ]. Recent progress in the characterization of barbiturate and other drug-binding receptors has been promising , However, as work has proceeded with the elucidation of elements involved in gene regulation, so has the appreciation of the complexity of the systems.

As an example, consider the Ah locus. The Ah receptor has now been extensively characterized but the list of involved partners continues to grow — and definition of the role of each component remains challenging.

A need exists for more understanding of mechanisms of regulation of enzymes involved in carcinogen metabolism. Just as important is an understanding of the influence of modulation on carcinogenesis and toxicity.

For instance, we are still not in a position to provide an explanation for the carcinogenicity and toxicity of dioxins Without such understanding, efforts to compare risk among species e.

humans are deficient Does induction of Ah-linked genes really imply increased risk from a chemical? Although regulatory agencies are concerned because of the example of dioxin, the answers still remain equivocal or, at the least, dependent upon the particular model under investigation , Concerns also exist about the significance of induction by barbiturates and peroxisome proliferators to carcinogenesis The basic question is whether high or low activity of a particular enzyme is related to a change in risk.

This type of work has become popular and there is good precedent for success in the paradigms of drug metabolism and P Programs such as the Environmental Genome Project have been set up to evaluate the contribution of gene polymorphisms to various risks.

Many issues need to be addressed, and there is considerable room for innovative approaches. approaches to determining the effect of a genetic change on the enzymatic or other function of the involved proteins 60 , , Another issue in this area is that of tissue localization and relevance to exposure.

For instance, we have made the point that the epoxidation of aflatoxin B 1 in the small intestine should be considered a detoxification event, in that it diverts the mycotoxin from the liver to cells that are readily sloughed The issue of tissue localization is a problem in that it shifts the field to measurement of RNA and proteins, which must be excised from humans in order to make analyses.

A related issue with polymorphisms is with genes that are not expressed in target tissues. Consideration of distribution kinetics of carcinogens and active metabolites and PBPK modes is needed vide supra.

Almost all of the experiments in the chemical carcinogenesis literature have been done with single compounds. This reductionist approach is not inappropriate and is certainly commended for understanding basic mechanisms. However, real exposure situations all involve mixtures and the approaches to dealing with these are difficult.

As an example from our own research, consider work on the genotoxicity of tobacco smoke condensate components The work was difficult because of the extremely inhibitory effect of tar components on P enzymes. What does this mean in terms of issues with smoking?

The literature contains considerations of strategies. More insight will be needed in this area, particularly as scientists try to relate work on carcinogen metabolism to molecular epidemiology and practical human issues.

This issue was addressed in a review 2. There is ample evidence in experimental animal models that altered carcinogen metabolism can have dramatic effects on tumor incidence , The concept that enzyme differences in humans can alter xenobiotic disposition and effects has very good precedence in the pharmaceutical industry, as mentioned earlier.

Therefore, there is great hope that similar effects will be seen with cancer. However, the epidemiology results to date have not been strong. Although the association of P 2D6 with lung cancer has been studied for many years, neither consistent epidemiology nor an experimental basis of a causal relationship have resulted 96 , 97 , Similar problems have been encountered with GSH transferases M1 and P1 , Although there have been some reports of altered cancer incidence related to Ps 1A1 and 1B1 , , the results cannot be interpreted in terms of any dramatic experimental differences between the allelic gene products — The evidence regarding N-acetyltransferase may be more compelling , One of the major problems in doing epidemiology studies of this type is assessment of the actual chemical exposure, whether an endogenous or xenobiotic chemical.

Linking variations in enzyme expression and catalytic activity to the endpoint of human cancer will remain a challenge for at least part of the next 20 years. Email: guengerich toxicology. I would like to dediacte this article to Prof. James A. Miller, who, with his late wife Elizabeth, really developed this area 4 , 49 , I also thank Dr Fred Kadlubar for his comments on the manuscript.

Work in the author's laboratory was supported in part by funds from the USPHS R35 CA and P30 ES and Hammons,G. In Guengerich,F. Mammalian Cytochromes P CRC Press, Boca Raton, FL, Vol.

Cancer Res. Academic Press, New York, Vols 1 and 2. Clowes Memorial Lecture. and Lee,F. Natl Acad. USA , 70 , — Drug Metab. and Jefcoate,C. and Pegg,A. and Guengerich,F. and Conney,A. and Ramel,C. Activation through conjugation with glutathione in vitro. USA , 80 , — and van Bladeren,P.

and Dekant,W. and Morrison,L. and Kadlubar,F. Carcinogenesis , 15 , — and Liem,A. Pharmacogenetics , 5 , S —S and Weston,A. Carcinogenesis , 21 , — and Ames,B.

and Nath,R. Carcinogenesis , 17 , — and Qiu,S. and Rogan,E. USA , 94 , — and Swenberg,J. American Chemistry Society, Washington, DC.

and Mermelstein,R. Health , C3 , — and Shimada,T. Carcinogenesis , 14 , — and El-Bayoumy,K. and Mason,R. and Beland,F. and Oesch,F. FEBS Lett. and Penning,T. Biochemistry , 21 , — Biochemistry , 22 , — and Momenteau,M. Ortiz de Montellano,P. In Ortiz de Montellano,P. Cytochrome P Plenum Press, New York, pp.

Evidence for a role of S -[2- N 7 -guanyl ethyl]glutathione as a mutagenic lesion formed from ethylene dibromide. USA , 90 , — and Claxton,L.

and Phillips,D. and Gupta,R. USA , 78 , — and Muramatsu,M. USA , 79 , — and Miller,J. Evidence for induction of enzyme synthesis in the rat by 3-methylcholanthrene.

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