Download Annual Review of Pharmacology and Toxicology Volume 45, 2005 by Arthur K. Cho, Terrence F. Blaschke, Paul A. Insel, Horace PDF

By Arthur K. Cho, Terrence F. Blaschke, Paul A. Insel, Horace H. Loh

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Extra info for Annual Review of Pharmacology and Toxicology Volume 45, 2005 (Annual Review of Pharmacology and Toxicology)

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This system allows the detection of HAA mutagenicity by recombinant human P450 without a need for rat liver fractions. These bacteria have also been genetically engineered to express S. typhimurium NAT, and the DNA nucleotide excision repair system has been inactivated (UvrABC) to improve the sensitivity (74, 77, 78). S. typhimurium tester strains have also been used to express human P450s that activate arylamines and HAAs (73, 79, 80). The E. coli strains overexpressing P450s and NAT have been used to characterize P450 1A2 allelic and random variants (81–84).

45:27-49. org by Universitaet Heidelberg on 10/01/05. For personal use only. sgm LaTeX2e(2002/01/18) P1: GCE GUENGERICH bind covalently to DNA. At least four enzyme systems are known to be involved in this secondary activation step in mammals: N-acetyltransferase (NAT), sulfotransferase, prolyl tRNA synthetase, and kinases, yielding reactive N-acetoxy, N-sulfonyloxy, N-prolyloxy, and N-phosphatyl esters, respectively (40–43). The N-hydroxy HAAs can react directly with DNA (32), but the reaction is facilitated when reactive ester derivatives undergo heterocyclic cleavage to yield reactive aryl nitrenium ion species, which preferentially react to form DNA adducts (Figure 2).

20:46–84 Sugimura T. 1985. Carcinogenicity of mutagenic heterocyclic amines formed during the cooking process. Mutat. Res. 150:33–41 Kato T, Ohgaki H, Hasegawa H, Sato S, Takayama S, et al. 1988. Carcinogenicity in rats of a mutagenic compound, 2amino-3,8-dimethylimidazo[4,5-f ]quinoxaline. Carcinogenesis 9:71–73 Nagao M, Sugimura T. 1993. Carcinogenic factors in food with relevance to colon cancer development. Mutat. Res. 290:43–51 Mueller GC, Miller JA. 1948. The metabolism of 4-dimethylaminoazobenzene by rat liver homogenates.

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