Metabolites of 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) in human urine after consumption of charbroiled or fried beef

Strickland, Paul T.; Qian, Zhengming; Friesen, Marlin D.; Rothman, Nathaniel; Sinha, Rashmi

doi:10.1016/s0027-5107(02)00163-x

Cited by 45 publications

(48 citation statements)

References 18 publications

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“…Although we could not examine whether higher PhIP-DNA adduct levels increased prostate cancer risk, a recent prospective human study found that the highest quintile of dietary PhIP intake was associated with a 1.2-fold increased risk of prostate cancer (10). Although several previous studies have examined biomarkers of PhIP exposure such as urine metabolites (34)(35)(36) and hair (37), only a few studies have attempted to correlate a biologically effective measure of PhIP exposure, PhIP-DNA adduct levels, in humans with self-reported exposure histories (32,38). Only a few studies have assayed for PhIP-DNA adducts in the tissues taken from the target organ in which the cancer occurred (32,39).…”

Section: Discussionmentioning

confidence: 92%

Grilled Meat Consumption and PhIP-DNA Adducts in Prostate Carcinogenesis

Tang¹,

Liu²,

Rundle

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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2-Amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) is the major heterocyclic amine generated from cooking meats at high temperatures, and dietary exposures have been shown to induce prostate cancer in rats. PhIP derives its carcinogenic potential through the formation of PhIP-DNA adducts. The purpose of this study was to examine whether self-reported consumption and preparation doneness of grilled meats were associated with PhIP-DNA adduct levels in prostate epithelial cells. The study population consisted of 268 AfricanAmerican and Caucasian men who underwent radical prostatectomy for prostate cancer. PhIP-DNA adducts in tumor and adjacent nontumor cells were measured using immunohistochemical methods, and dietary meat intake information was based on food frequency questionnaires. Data were analyzed using multivariate linear regression models. After adjusting for age at prostatectomy and race, grilled meat consumption (P = 0.002) was significantly associated with higher adduct levels in tumor cells, but this association seemed to be primarily due to consumption of grilled red meats (P = 0.001) as opposed to grilled white meat consumption (P = 0.15). Among the specific food items, grilled hamburger consumption had the most significant association with adduct level in tumor cells (P = 0.002). Similar trends in positive associations with grilled meat consumption and adduct levels were observed in nontumor cells, but none of these associations reached statistical significance. Our results suggest that dietary interventions targeted at lower consumption of grilled red meats may reduce prostate cancer risk via the PhIP prostate carcinogenic pathway. (Cancer Epidemiol Biomarkers Prev 2007;16(4):803 -8)

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Section: Discussionmentioning

confidence: 92%

Grilled Meat Consumption and PhIP-DNA Adducts in Prostate Carcinogenesis

Tang¹,

Liu²,

Rundle

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…HCAs are absorbed and metabolized by humans, and have a half-life of less than 12 h [13]. One way of estimating the recent exposure is by analysing HCAs and their metabolites in human urine samples to obtain data on the capacity of individuals to bioactivate and detoxify HCAs [14][15][16]. Urinary 2-amino-1-methyl-6-(5-hydroxy)-phenylimidazo [4,5-b]pyridine (5-OHPhIP) was found to be directly related to the ultimate electrophile nitrenium ion that form DNA-adducts at the guanine base, and suggested as a plausible biomarker of the genotoxic dose of PhIP [17][18][19].…”

Section: Pyridine;mentioning

confidence: 99%

Hollow fibre‐supported liquid membrane extraction and LC‐MS/MS detection for the analysis of heterocyclic amines in urine samples

Busquets¹,

Jönsson²,

Frandsen³

et al. 2009

Molecular Nutrition Food Res

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Heterocyclic amines (HCAs) are potent mutagens/carcinogens to which humans are frequently exposed through the consumption of cooked meat and fish food. The effect of normal intake of HCAs and their role in the aetiology of human cancer is unknown. To some extent, limitations of the existing analytical methods in monitoring the low levels of HCAs in biological samples have hindered obtaining conclusive results. In this study, a method for the analysis of HCAs in human urine has been studied to detect HCAs and metabolites at levels resulting from consumption of food cooked at ordinary conditions. The analytical method consisted of extraction and clean-up by the novel technique liquid-phase microextraction combined with LC-MS/MS. The effect of pH during the extraction and hydrolysis step was examined. High sensitivity was achieved when the extraction was performed in raw urine adjusted to pH 5.5, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine being detected from 2 pg/g urine, levels comparable with a normal exposure. Good reproducibility and repeatability was obtained for 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, below 9% using isotopic dilution. The performance of the method on 9H-pyrido[3,4-b]indole, 2-amino-1-methyl-6-(4'-hydroxyphenyl)imidazo[4,5-b]pyridine and 2-amino-1-methyl-6-(5-hydroxy)phenylimidazo[4,5-b]pyridine was also studied.

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“…Metabolism of some HAs appears to be extensive as it was observed that radiolabeled HAs were rapidly eliminated with only a small amount excreted unchanged in urine [126][127][128]. In contrast, it was reported that for PhIP, wide interindividual differences were observed for the proportion of ingested dose being excreted as urinary metabolites, and this could be brought about by factors such as absorption or metabolic rates in addition to level of exposure [129]. Such comparison between the amounts of metabolites in urine and the original amounts ingested has also been the usual approach for assessing HA bioavailability in humans [116].…”

Section: Bioavailability and Bioactivationmentioning

confidence: 99%

Heterocyclic amines: Chemistry and health

Cheng¹,

Chen²,

Wang³

2006

Molecular Nutrition Food Res

102

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Heterocyclic amines (HAs) occur at the ppb range in foods. Most of them demonstrate potent mutagenicity in bacteria mutagenicity test, and some of them have been classified by the International Agency for Research on Cancer as probable/possible human carcinogens. Their capability of formation even during ordinary cooking practices implies frequent exposure by the general public. Over the past 30 years, numerous studies have been stimulated aiming to alleviate human health risk associated with HAs. These studies contribute to the understanding of their formation, characterization, and quantification in foods; their mutagenesis/carcinogenesis, mechanisms of antimutagenesis by chemical or phytogenic modulators; and strategies to inhibit their formation. The chemistry of HAs, their implications in human health, factors influencing their formation, and feasible ways of suppression will be briefly reviewed. Their occurrence in trace amounts in foods necessitates continuous development and amelioration of analytical techniques. Various inhibitory strategies, ranging from modifying cooking conditions to incorporation of different modulators, have been developed. This will remain one of the foremost areas of research in the field of food chemistry and safety.

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Metabolites of 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) in human urine after consumption of charbroiled or fried beef

Cited by 45 publications

References 18 publications

Grilled Meat Consumption and PhIP-DNA Adducts in Prostate Carcinogenesis

Grilled Meat Consumption and PhIP-DNA Adducts in Prostate Carcinogenesis

Hollow fibre‐supported liquid membrane extraction and LC‐MS/MS detection for the analysis of heterocyclic amines in urine samples

Heterocyclic amines: Chemistry and health

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