Heterocyclic aromatic amines in human urine following a fried meat meal

Reistad, R.; Rossland, O.J.; Latva‐Kala, Kyösti; Rasmussen, T.; Vikse, Rose; Becher, Georg; Alexander, Jan

doi:10.1016/s0278-6915(97)00112-9

Cited by 101 publications

(107 citation statements)

References 21 publications

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“…Our results point to UGT1A1 as the key enzyme involved in the hepatic formation of this metabolite as well as in the formation of N-OH-PhIP-N 3 G also found in urine at significant levels. 11,12,42,43 It was critical to assess whether different UGT enzymes were involved particularly in the formation of N 2 G and N 3 G. N 2 -glucuronides are resistant to ␤-glucuronidases present in the intestinal flora and are readily excreted into the urine. In contrast, N 3 -glucuronides can be deconjugated by bacterial ␤-glucuronidases back to N-OHPhIP, 44 and re-conjugation with N-acetyltransferases or sulfotransferases can possibly occur in the gastrointestinal tract to form highly reactive compounds capable of binding DNA.…”

Section: Discussionmentioning

confidence: 99%

“…8 After PhIP exposure, the main metabolite in urine after PhIP exposure is N-OH-PhIP-N 2 glucuronide, followed by PhIP-N 2 -glucuronide, N-OH-PhIP-N 3 glucuronide, and 4Ј-PhIP-sulfate. [10][11][12][13] Controlled feeding studies revealed a significant variation in the excretion of urinary PhIP and its polar metabolites, indicating that there are substantial interindividual differences in glucuronidation capacity. 12,[14][15][16] Multiple genes encoding for glucuronidation enzymes display polymorphic distribution.…”

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confidence: 99%

“…[10][11][12][13] Controlled feeding studies revealed a significant variation in the excretion of urinary PhIP and its polar metabolites, indicating that there are substantial interindividual differences in glucuronidation capacity. 12,[14][15][16] Multiple genes encoding for glucuronidation enzymes display polymorphic distribution. 17 UGT genetic factors might determine the host capacity to detoxify HCA carcinogens, thus modifying their exposure to HCAs and potentially their risk of developing cancer.…”

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UGT1A1 polymorphisms are important determinants of dietary carcinogen detoxification in the liver

et al. 2005

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PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-f]pyridine), the most abundant heterocyclic amine in diet, is involved in the etiology of cancer. PhIP and its carcinogenic metabolite Nhydroxy-PhIP (N-OH-PhIP) are extensively conjugated by UDP-glucuronosyltransferase (UGTs) with wide variability. This study aimed to determine the genetic influence of UGTs on the hepatic detoxification of this carcinogen. The formation of N-OH-PhIP glucuronides was studied in 48 human liver samples by mass spectrometry. Liver samples were genotyped for common polymorphisms and correlated with UGT protein levels and N-OH-PhIP glucuronidation activities. The formation of four different N-OH-PhIP glucuronide metabolites was observed in all livers. The major metabolite was N-OH-PhIP-N 2 -glucuronide (N 2 G), which is the primary metabolite found in human urine, and showed a high interindividual variability (up to 28-fold). Using an heterologous expression system, the bilirubin-conjugating UGT1A1 enzyme was identified among all known UGTs (n ‫؍‬ 16) as the predominant enzyme involved. The significant correlation between UGT1A1 protein content and formation of N 2 G (Rs ‫؍‬ 0.87; P < .0001) suggests a critical role for UGT1A1 in the hepatic metabolism of this carcinogen. UGT1A1 expression was strongly determined by the presence of the common promoter polymorphisms, UGT1A1*28 (TATA box polymorphism) (P ‫؍‬ .0031), ؊3156G/A (P ‫؍‬ .0006) and ؊3279G/T (P ‫؍‬ .0017), and rates of N 2 G were indeed correlated with these polymorphisms (P < .05), whether analyzed individually or in combination (haplotypes). In conclusion,

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UGT1A1 polymorphisms are important determinants of dietary carcinogen detoxification in the liver

et al. 2005

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“…Five pooled urine samples derived from the Shanghai Cohort study were measured for urinary HAA using previously published acid or base hydrolysis steps for cleavage of phase II conjugates of the parent amines (26,(31)(32)(33)(34) before the tandem solvent-SPE procedure. The acid or base hydrolysis was conducted by addition of 10 N HCl or 10 N NaOH (0.22 mL) to urine (1 mL) and heating at 70jC for 6 h. After cooling, the acid-treated samples were made alkaline with 10 N NaOH (0.32 mL).…”

Section: Methodsmentioning

confidence: 99%

Tobacco Smoking and Urinary Levels of 2-Amino-9H-Pyrido[2,3-b]Indole in Men of Shanghai, China

Turesky

Yuan²,

Wang

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Carcinogenic heterocyclic aromatic amines (HAA) are formed in cooked meats, poultry, and fish and arise in tobacco smoke. We measured the concentrations of four prevalent HAAs in spot urine samples collected at baseline from 170 participants of the Shanghai Cohort study, a population-based cohort study of adult men recruited during 1986 to 1989 in Shanghai, China. Sixteen (18.6%) of 86 nonsmokers were positive for urinary 2-amino-9H-pyrido[2,3-b]indole (AAC) versus 41 (48.8%) of 84 cigarette smokers; the difference was statistically significant (P < 0.001). The number of cigarettes smoked per day was positively and significantly related to urinary levels of AAC in study subjects (P < 0.001); the mean level among nonsmokers was 2.54 ng/g creatinine, whereas the means for light (1-19 cigarettes per day) and heavy (20+ cigarettes per day) smokers were 7.50 and 11.92 ng/g creatinine, respectively. 2-Amino-3,4,8-trimethylimidazo [4,5-f] quinoxaline was undetected in the urine of the 170 subjects. Only 5 (2.9%) and 6 (3.5%) subjects, respectively, showed detectable levels of urinary 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine and 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline, and smoking status was unrelated to levels of either HAA. Quantitative measurements of HAAs in commonly eaten pork and chicken dishes in Shanghai showed low concentrations of HAAs (<1 ng/g meat). Our data indicate that AAC represents a major HAA exposure in adult men of Shanghai, China, and that tobacco smoke is an important point source of their AAC exposure. (Cancer Epidemiol Biomarkers Prev 2007;16(8):1554 -60)

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“…The fact that PhIP or its metabolites were found in human urine or milk [11][12][13][14][15][16] and that PhIP-DNA adducts could be detected in human urine, breast epithelial cells [17][18][19] suggests that humans are exposed to PhIP on a daily basis. The mean exposure level to PhIP has been estimated to be 5.3-20 ng/kg/day for the US population 20) and 72 ng/day/person for the Stockholm population.…”

Section: Discussionmentioning

confidence: 99%

High susceptibility of the ACI and spontaneously hypertensive rat (SHR) strains to 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) prostate carcinogenesis

et al. 2003

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rostate cancer is the most common non-cutaneous cancer in men in Western countries such as Europe and the United States 1) and its prevalence has also been increasing in Japan, 2) concomitantly with change in life style. Androgen ablation therapy is widely accepted and carried out for prostate cancers because androgens are essential for the development and growth of normal prostate and prostate cancer cells.3) However, outgrowth of hormone-independent cancer cells occurs within 1-2 years and eventually leads to a fatal outcome in many cases. 4)In vivo rat model systems for prostate cancer have been established in our laboratory. In these animal models, 3,2′-dimethyl-4-aminobiphenyl (DMAB) induces androgen-dependent non-invasive carcinomas in the ventral prostate while additional long-term treatment with testosterone propionate (TP) causes development of invasive and metastasizing androgen-independent carcinomas in the dorsolateral and anterior prostate and seminal vesicles.5-7) We have found that 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP), an environmental heterocyclic amine, also induces prostate adenocarcinomas in the ventral lobe in male F344 rats.8) This might be an especially suitable model to investigate risk factors or chemoprevention of prostate cancer, because PhIP is naturally occurring carcinogen which is produced during the ordinary cooking process of meat and fish 9) and humans are often exposed to PhIP in ordinary daily life via cooked food, wine, beer and cigarette-smoke.In the present study, we investigated strain differences in susceptibility of male rats to PhIP-induction of prostate carcinogenesis. Materials and MethodsChemicals and animals. PhIP hydrochloride with a purity of >99.9% was obtained from the Nard Institute (Osaka). Male 6-week-old F344 (F344/DuCrj), Spontaneously Hypertensive Rat (SHR) (SHR/NCrj), Lewis (LEW/Crj), Brown Norway (BN) (BN/Crj), Sprague-Dawley (SD)(Crj:CD(SD)) and Wistar (Crj:Wistar) rats were purchased from Charles River Japan, Inc. (Atsugi). ACI (ACI/N Slc) rats were from Nihon SLC (Shizuoka). All were housed 3/cage on wood-chip bedding in an air-conditioned animal room at 23±2°C and 50±10% humidity. Food (Oriental MF, Oriental Yeast Co., Tokyo) and tap water were available ad libitum. Experiment 1. Twelve rats for each group received PhIP in the diet at a dose of 400 ppm for 20 weeks starting at the age of 10 weeks. One of the SD rats and three of the Wistar rats were eliminated from the experimental numbers, because of their accidental death. The experiment was terminated at week 54 and the animals were subjected to complete autopsy. All accessory sex organs were examined for gross abnormalities and fixed in 10% buffered formalin. After fixation, the ventral prostate was removed from the base of the bladder neck and the entire organ was weighed. For tissue preparation of the accessory sex organs, one sagittal slice through the ventral prostate, two sagittal samples of the dorsolateral prostate including the urethra, and four transverse slices from ea...

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Heterocyclic aromatic amines in human urine following a fried meat meal

Cited by 101 publications

References 21 publications

UGT1A1 polymorphisms are important determinants of dietary carcinogen detoxification in the liver

UGT1A1 polymorphisms are important determinants of dietary carcinogen detoxification in the liver

Tobacco Smoking and Urinary Levels of 2-Amino-9H-Pyrido[2,3-b]Indole in Men of Shanghai, China

High susceptibility of the ACI and spontaneously hypertensive rat (SHR) strains to 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) prostate carcinogenesis

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