1991
DOI: 10.1093/carcin/12.10.1839
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Metabolic activation of carcinogenic heterocyclic aromatic amines by human liver and colon

Abstract: The metabolic activation of the food-borne rodent carcinogens 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) was compared with that of the known human carcinogen 4-aminobiphenyl (ABP), using human liver microsomes, human and rat liver cytosols, and human colon cytosol. All of these aromatic amines were readily activated by N-hydroxylation wi… Show more

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Cited by 336 publications
(283 citation statements)
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“…The NAT1 genotype NATI*4/NAT1*15 was less frequent than expected, if random distribution is assumed, in individuals with a slow NAT2 genotype in both the control and the cancer groups. This may represent genetic linkage between NATI and NAT2, which are closely related and have overlapping substrate specificity (Turesky et al, 1991). This linkage may confound studies of NAT1 and NAT2 polymorphism with disease susceptibility.…”
Section: Resultsmentioning
confidence: 99%
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“…The NAT1 genotype NATI*4/NAT1*15 was less frequent than expected, if random distribution is assumed, in individuals with a slow NAT2 genotype in both the control and the cancer groups. This may represent genetic linkage between NATI and NAT2, which are closely related and have overlapping substrate specificity (Turesky et al, 1991). This linkage may confound studies of NAT1 and NAT2 polymorphism with disease susceptibility.…”
Section: Resultsmentioning
confidence: 99%
“…Polymorphisms of NAT2 that result in slow acetylation of metabolites have been associated with bladder cancer (Risch et al, 1995) and, conversely, fast acetylators may be more common in colorectal cancer and some types of breast cancer (Lang et al, 1986;Agundez et al, 1995). However these associations are weak and are not supported by all studies (Bell et al, 1995a;Hubbard et al, 1997).A potentially confounding factor in these assessments is the contribution of NATI, a closely related enzyme that shares some substrate specificity with NAT2 (Hein et al, 1992), which is expressed at higher levels than NAT2 in colonic epithelial cells (Turesky et al, 1991). Recent studies have shown that NATI is also polymorphic and 15 variants have been detected in animal and human gene sequences Weber and Vatsis, 1993;Grant et al, 1997).…”
mentioning
confidence: 99%
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“…Another predominant HA found in cooked meats, 2 -amino-3,8-dimethylimidazo [ 4,5-f] quinoxaline (MeIQx), causes tumors at multiple sites in rats and mice Bogen, 1994 ). HAs are metabolically activated by P450 and N -acetyltranserase enzymes, and activated forms are observed to bind covalently to DNA at sites including tissues (including prostate ) in which HAs induce cancer in rats (Thorgeirsson, 1984;Thorgeirsson et al, 1983;Rosenkranz and Mermeistein, 1985;Sato et al, 1986;Kato and Yamazoe, 1987;Snyderwine and Battula, 1989;McManus et al, 1990;Turesky et al, 1991;Davis et al, 1993;Kaderlik et al, 1994a,b;Takahashi et al, 1998;Schut and Snyderwine, 1999 ).…”
Section: Introductionmentioning
confidence: 99%
“…A recent review describes the nucleotide and aminoacid changes associated with various alleles and deduced phenotype from genotype. It also summarized results of molecular epidemiologic studies assessing the association of NAT1 and NAT2 genotypes with cancer risk of bladder, colon, breast, lung, head and neck and prostate (12,13).…”
Section: Introductionmentioning
confidence: 99%