Longitudinal Study of Urinary Phenanthrene Metabolite Ratios: Effect of Smoking on the Diol Epoxide Pathway

Hecht, Stephen S.; Chen, Menglan; Yoder, Andrea R.; Jensen, Joni; Hatsukami, Dorothy K.; Le, Chap T.; Carmella, Steven G.

doi:10.1158/1055-9965.epi-05-0396

Cited by 44 publications

(39 citation statements)

References 26 publications

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“…We do not know if the PheT/HOPhe ratios were stable over time in our 346 subjects. In a previous study, we measured urinary phenanthrene metabolites in 12 smokers who provided samples daily for 7 days and then weekly for 6 weeks (30). PheT/HOPhe ratios were relatively stable in some subjects but quite variable in others.…”

Section: Discussionmentioning

confidence: 99%

“…We believe that carcinogen metabolite phenotyping, which is the actual measurement of metabolites resulting from PAH activation and detoxification, is a more reliable way to identify those smokers who efficiently metabolically activate PAH and therefore may be at higher risk for lung cancer. We are pursuing this line of research by quantifying phenanthrene metabolites in human urine (28)(29)(30). Phenanthrene is the simplest PAH molecule with a bay region, a feature closely associated with carcinogenicity (8,31).…”

Section: Introductionmentioning

confidence: 99%

“…Phenanthrene and BaP are both metabolized to phenols (HOBaP and HOPhe), which are considered to be detoxification products (7,33). In previous studies, we have developed methods for quantifying PheT and HOPhe in human urine and investigated the longitudinal stability of these measures in smokers and nonsmokers (28)(29)(30). We propose that the ratio PheT/HOPhe will be characteristic of an individual and that smokers with higher PheT/HOPhe ratios should be at higher risk for lung cancer.…”

Section: Introductionmentioning

confidence: 99%

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Comparison of Polymorphisms in Genes Involved in Polycyclic Aromatic Hydrocarbon Metabolism with Urinary Phenanthrene Metabolite Ratios in Smokers

Hecht

Carmella

Yoder

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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The hypothesis that interindividual differences among smokers in the metabolism of polycyclic aromatic hydrocarbons (PAH) are related to lung cancer risk has been extensively investigated in the literature. These studies have compared lung cancer risk in groups of smokers with or without polymorphisms in genes involved in PAH metabolism. We believe that carcinogen metabolite phenotyping, involving the actual measurement of PAH metabolites, would be a better way to investigate differences in lung cancer risk. With this goal in mind, we have developed methods for quantifying phenanthrene metabolites in urine. Phenanthrene is the simplest PAH with a bay region, a feature closely associated with carcinogenicity. The urinary metabolite r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT) is a measure of metabolic activation, whereas phenanthrols (HOPhe) are a measure of detoxification. In this study, we quantified urinary PheT/HOPhe ratios in 346 smokers who were also genotyped for 11 polymorphisms in genes involved in PAH metabolism: CYP1A1MspI, CYP1A1I462V, CYP1B1R48G, CYP1B1A119S, CYP1B1L432V, CYP1B1N453S, EPHX1Y113H, EPHX1H139R, GSTP1I105V, GSTP1A114V, and GSTM1 null. The geometric mean molar PheT/3-HOPhe ratio was 4.08 (95% confidence interval, 3.79-4.39). Ten percent of the smokers had PheT/3-HOPhe ratios of z9.90. We found a significant association between the presence of the CYP1A1I462V polymorphism and high PheT/3-HOPhe ratios (P = 0.02). This effect was particularly strong in females and in combination with the GSTM1 null polymorphism. In contrast, the CYP1B1R48G and CYP1B1A119S polymorphisms were associated with significantly lower PheT/3-HOPhe ratios, particularly in Blacks. There were no consistent significant effects of any of the other polymorphisms on PheT/3-HOPhe ratios. The highest 10% of PheT/3-HOPhe ratios could not be predicted by the presence of any of the 11 polymorphisms individually or by certain combinations. The effects of the CYP1A1I462 polymorphism observed here, particularly in combination with GSTM1 null, are quite consistent with reports in the literature. However, the results of this study indicate that genotyping is not an effective way to predict PAH metabolism at least as represented by PheT/HOPhe ratios.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Comparison of Polymorphisms in Genes Involved in Polycyclic Aromatic Hydrocarbon Metabolism with Urinary Phenanthrene Metabolite Ratios in Smokers

Hecht

Carmella

Yoder

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…PheT is a good biomarker of uptake and metabolic activation of phenanthrene, a typical PAH, and the simplest PAH with a bay region, a feature closely associated with carcinogenicity. In previous studies, we have measured PheT in the urine of smokers and nonsmokers (10,11). However, plasma and serum are more frequently used than urine in molecular epidemiology studies.…”

Section: Introductionmentioning

confidence: 99%

Combined Analysis of r-1,t-2,3,c-4-Tetrahydroxy-1,2,3,4-Tetrahydrophenanthrene and 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanol in Smokers' Plasma

Carmella

Yoder

Hecht

2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Polycyclic aromatic hydrocarbons (PAH) and tobaccospecific nitrosamines, such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), are widely accepted to be two important types of lung carcinogens in cigarette smoke. In this study, we have developed a method to estimate individual uptake of these compounds by quantifying r -1,t -2,3,c -4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in 1 mL of smokers' plasma. PheT and NNAL are biomarkers of PAH and NNK uptake, respectively. [D 10 ]PheT and [pyridine-D 4 ]NNAL were added to plasma as internal standards. The plasma was treated with B-glucuronidase to release any conjugated PheT and NNAL. The analytes were enriched by solid-phase extraction on a mixed mode cation exchange cartridge and the PheT fraction was further purified by high-performance liquid chromatography. The appropriate fractions were analyzed by gas chromatography-negative ion chemical ionization-mass spectrometry for PheT and liquid chromatography-electrospray ionization-mass spectrometry for NNAL. The method was sensitive (limits of quantitation: PheT, 13 fmol/mL; NNAL, 3 fmol/mL), accurate, and precise. Levels of PheT and NNAL in plasma from 16 smokers averaged 95 F 71 and 36 F 21 fmol/mL, respectively, which are f1% to 2% of the amounts found in urine. This method should be useful in molecular epidemiology studies of carcinogen uptake and lung cancer in smokers. (Cancer Epidemiol Biomarkers Prev 2006;15(8):1490 -4)

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“…That is why one of the possible explanations is the activation of other metabolic mechanisms (e.g. diol-epoxide mechanism) rather than only direct detoxification of pyrene to 1-OHP at higher external exposures (26).…”

Section: -Ohpmentioning

confidence: 99%

The Relations between Polycyclic Aromatic Hydrocarbons Exposure and 1-OHP Levels as a Biomarker of the Exposure

Klöslová¹,

Drimal

Balog

et al. 2016

Cent Eur J Public Health

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SUMMARYBackground and Aim: Polycyclic aromatic hydrocarbons (PAHs) are the products of incomplete combustion or pyrolysis of various organic materials. Their ubiquity in the environment leads to measurable levels of exposure. However, the exposure varies strongly between different regions in Europe. Some PAHs with four or more rings are suspected to be human carcinogens. Therefore, the occupational and/or environmental exposure to PAHs may cause a significant health risk. The aim of the study was to evaluate current levels of PAH exposure in defined groups of workers.Methods: The industrial sites selected in this survey involved PAHs originating from coal tar pitch, carbon black, bitumen, and rubber fumes. Based on the historical data, the sites were expected to exhibit quantifiable levels of exposure to PAHs. The total study population consisted of 139 persons: 108 workers (85 males and 23 females) occupationally exposed in aluminium production, the production of graphite electrodes, road construction, or the rubber forming industry and 31 control individuals in two groups.Results: The highest concentrations -8-hour time-weighted average (TWA) levels (sum of 16 components according to the EPA list), as expected, were found in the aluminium production plant (55.15 µg.m −3 ) and production of graphite electrodes (54.25 µg.m −3 ). The lowest concentrations were found in personal air samples of road construction workers (1.93 µg.m −3 ). The concentrations of 1-hydroxypyrene as a pyrene metabolite (1-OHP) in the urine of the exposed group of workers were found in levels 0.74 µmol.mol −1 creatinine before the exposure and 2.27 µmol.mol −1 creatinine after the exposure (arithmetic mean values). 1-OHP concentrations in post-shift urine samples were highly correlated with the total airborne PAHs concentrations and pyrene concentrations in air. The correlation coefficients (r S ) between 1-OHP concentration and pyrene or total PAHs in air were 0.710 and 0.752 (p < 0.05). This statistical analysis confirmed the effect of the occupational exposure to PAHs and pyrene on body burden in workers. However, a modifying effect of gender, smoking habits, dietary intake, genetically modified metabolism, and the use of medication on the toxicokinetics of pyrene was not determined as significant.Conclusion: Based on the results a strong correlation between the concentration of 1-OHP in urine as an exposure biomarker and the concentration of pyrene or PAH was affirmed.

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Longitudinal Study of Urinary Phenanthrene Metabolite Ratios: Effect of Smoking on the Diol Epoxide Pathway

Cited by 44 publications

References 26 publications

Comparison of Polymorphisms in Genes Involved in Polycyclic Aromatic Hydrocarbon Metabolism with Urinary Phenanthrene Metabolite Ratios in Smokers

Comparison of Polymorphisms in Genes Involved in Polycyclic Aromatic Hydrocarbon Metabolism with Urinary Phenanthrene Metabolite Ratios in Smokers

Combined Analysis of r-1,t-2,3,c-4-Tetrahydroxy-1,2,3,4-Tetrahydrophenanthrene and 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanol in Smokers' Plasma

The Relations between Polycyclic Aromatic Hydrocarbons Exposure and 1-OHP Levels as a Biomarker of the Exposure

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