Heterocyclic amines: evaluation of their role in diet associated human cancer

Gooderham, Nigel J.; Murray, Stephen A.; Lynch, Anthony M.; Edwards, Robert J.; Yadollahi-Farsani, Masoud; Bratt, Charlotte; Rich, Kim J.; Zhao, Kaicun; Murray, Bernard P.; Bhadresa, Sanjeev; Crosbie, Sarah J.; Boobis, Alan R.; Davies, Donald S.

doi:10.1046/j.1365-2125.1996.37513.x

Cited by 41 publications

(21 citation statements)

References 7 publications

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“…Also, CYP1A2 activates several aromatic amines and thus is a key enzyme implicated in chemical carcinogenesis. 20 A common A to C in the CYP1A2*F (rs762551) SNP has been associated with decreased enzyme inductivity and enzymatic activity, resulting in a slower metabolism of caffeine. 21,22 The CC genotype for CYP1A2*F was also significantly associated with lower serum estradiol levels during the luteal phase.…”

Section: Discussionmentioning

confidence: 99%

Genetic polymorphisms of estrogen metabolizing enzyme and breast cancer risk in Thai women

Sangrajrang

Sato²,

Sanada³

et al. 2009

Intl Journal of Cancer

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Estrogen and its metabolites are believed to play important roles in breast cancer, and its determinants include both genetic and lifestyle factors. The objective of the study is to investigate the association of breast cancer risk in Thailand with genetic polymorphisms in several genes involved in estrogen synthesis and metabolism. Five hundred and seventy patients with histopathologically confirmed breast cancer and 497 controls were included in the present study. Forty single nucleotide polymorphisms (SNPs) in the CYP1A1, CYP1A2, CYP1B1, CYP17, CYP19, CYP2C9, CYP2C19, AhR, ESR1, PGR, ERRG, COMT, HSD17B1, HSD17B2, EPHX1 and NQO1 genes were genotyped. Association of genotypes with breast cancer risk was evaluated using multivariate logistic regression, which suggested an altered risk for the following SNPs [gene, odds ratio (OR) . In addition, a stratified analysis by menopausal status indicated that the association of the CYP1A2 (rs762551) and CYP17 (rs743572) polymorphisms with breast cancer risk were mainly evident in premenopausal, while ERRG (rs1857407) was significant in postmenopausal women. These findings suggest that CYP1A2, CYP2C19, AhR, ERRG and CYP17 polymorphisms may play an important role in estrogen metabolism and modify individual susceptibility to breast cancer in Thai women. ' UICCKey words: breast cancer; estrogen metabolizing enzyme; single nucleotide polymorphisms Much of the variability in global breast cancer rates has been attributed to country-specific differences in the prevalence of risk factors that determine lifetime exposure to estrogen. Comparatively younger ages at menarche, older ages at first birth and/or menopause and a higher prevalence of postmenopausal obesity have been proposed as explanations for the disparate breast cancer incidence rates among American Caucasian (97/100,000) and Asian women (27/100,000).1,2 Cross cultural differences in height, diet, alcohol consumption and exogenous estrogen use are also believed to contribute to international differences, but to a lesser extent. 3,4 Age-specific breast cancer incidence also varies between high-and low-risk countries: the mean age at diagnosis in developing countries is lower than that for European and American populations.It can be hypothesized that estrogen metabolites contribute to the activation of the estrogen receptor and the generation of DNAdamaging molecular species. 5 The genes involved in the disposition of female sex hormones are well known, and include COMT (catechol-O-methyltransferase), HSD17B1 (17 b-hydroxysteroid dehydrogenase type 1), HSD17B2, ESR a (estrogen receptor a), PGR (progesterone receptor), ERRG (estrogen-related receptor g), NQO1 (NADPH quinine oxoreductase), EPHX1 (epoxide hydrolase), AhR (aryl hydrocarbon receptor a) and members of the cytochrome P450 family including CYP1A1, CYP1A2, CYP1B1, CYP17, CYP19, CYP2C9 and CYP2C19.Because Asian women have, on average, a 20% lower serum estradiol level than Western women, 6 it is possible that the effects of genetic polymorphisms of estrogen-...

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Section: Discussionmentioning

confidence: 99%

Genetic polymorphisms of estrogen metabolizing enzyme and breast cancer risk in Thai women

Sangrajrang

Sato²,

Sanada³

et al. 2009

Intl Journal of Cancer

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“…It is important to note that the apparent tissue selectivity of PhIP-induced mutation (colon > liver) is consistent with PhIP's reported carcinogenicity; i.e. as an intestinal rather than hepatic carcinogen 14 .…”

Section: Discussionmentioning

confidence: 72%

“…This is followed by subsequent phase II metabolism, by enzymes such as Nacetyltransferase 13 . Both of these metabolic steps are carried out with greater efficiency in human hepatic tissue than that of mice and rats 14 .…”

Section: Introductionmentioning

confidence: 99%

The mutagenic effects of 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine in Muta™Mouse colon is attenuated by resveratrol

2014

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Epidemiology studies show that consumption of certain naturally occurring chemicals (generally plant-derived) can protect against the development of cancer (chemoprevention).Resveratrol, a phytoalexin found in foods such as grapes and wine as a glucoside , is one such chemical. Our group has previously shown that treating mammalian cells with resveratrol aglycone can reduce the mutagenicity of the cooked meat-derived carcinogens 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP). However, the anti-mutagenic effect of resveratrol in vivo has not been previously reported. In this study, daily treatment of resveratrol up to 1000µg/kg for 10 days was well tolerated in Muta TM Mouse mice. Treating Muta TM Mouse mice with the meat carcinogen 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine induced mutation in the colon. Co-treatment of resveratrol and PhIP reduced the mutation frequency induced by PhIP in the colon by about 25% in a treatment group of mixed male and females. Analysing males and females separately revealed a sex difference in the response to PhIP and to the effect of resveratrol on PhIP-induced mutagenicity. In males compared to females, PhIP was a more potent colonic mutagen and resveratrol was more effective at attenuating the mutagenic response ( ~35% in males but only 9% in females). The reason for this sex difference in both PhIP mutagenicity and response to resveratrol is not clear. However, resveratrol treatment was also shown to powerfully inhibit ethoxyresorufin-O-deethylase activity in vivo, indicating that the antimutagenic affects are likely linked to metabolic activation of PhIP.These data suggest that resveratrol has anti-mutagenic effects in vivo, supporting its potential to act as a chemopreventative.

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“…These include dietary and nutritional factors, hormonal changes in the body, ingestion of medicinal agents, and exposure to environmental factors [7]. Diet is an environmental factor that greatly influences the activity of P450 1A2.…”

mentioning

confidence: 99%

“…P450 1A2 is also responsible for the electrophilic activation of aromatic and heterocyclic amines and polycyclic aromatic hydrocarbons [5,6]. Heterocyclic amines, produced during the cooking of red meat for instance, are metabolized by P450 1A2 to electrophilic metabolites that have been shown to cause DNA mutations and cancer [7,8]. Polycyclic aromatic hydrocarbons, also present in high concentrations in charbroiled meats as well as tobacco smoke, serve both as substrates for and inducers of P450 1A2 activity [9].…”

mentioning

confidence: 99%

HPLC determination of caffeine and paraxanthine in urine: An assay for cytochrome P450 1A2 activity

Furge

Fletke

2007

Biochem Molecular Bio Educ

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Cytochrome P450 enzymes are a family of heme-containing proteins located throughout the body with roles in metabolism of endogenous and exogenous compounds. Among exogenous compounds, clinically relevant pharmaceutical agents are nearly all metabolized by P450 enzymes. However, the activity of the different cytochrome P450 enzymes varies among individuals and, therefore, so does drug efficacy as well as susceptibility to side effects and toxicity. Thus, assessing P450 activity is of great interest in drug development and clinical pharmacology. This study investigates the phenotyping of a single P450 activity by analyzing urine samples using isocratic reverse-phase HPLC. Specifically, the activity of human P450 1A2, which converts caffeine into paraxanthine, can be investigated by measuring the change in caffeine and paraxanthine concentrations in urine over time following a single dose of caffeine. There is an observable relationship between caffeine intake and paraxanthine formation that varies among individuals. This laboratory exercise provides a means for simple assessment of P450 1A2 metabolic activity using an HPLC method without additional extraction or purification steps and introduces students to the complexities of individualized medicine as well as the basic biochemical techniques of sample preparation and quantitative HPLC. Furthermore, students may design and test their own hypothesis using these methods.

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Heterocyclic amines: evaluation of their role in diet associated human cancer

Cited by 41 publications

References 7 publications

Genetic polymorphisms of estrogen metabolizing enzyme and breast cancer risk in Thai women

Genetic polymorphisms of estrogen metabolizing enzyme and breast cancer risk in Thai women

The mutagenic effects of 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine in Muta™Mouse colon is attenuated by resveratrol

HPLC determination of caffeine and paraxanthine in urine: An assay for cytochrome P450 1A2 activity

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