Journal Article

Role of human <i>N</i>-acetyltransferases, NAT1 or NAT2, in genotoxicity of nitroarenes and aromatic amines in <i>Salmonella typhimurium</i> NM6001 and NM6002

Yoshimitsu Oda, Hiroshi Yamazaki and Tsutomu Shimada

in Carcinogenesis

Volume 20, issue 6, pages 1079-1083
Published in print June 1999 | ISSN: 0143-3334
Published online June 1999 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/20.6.1079
Role of human N-acetyltransferases, NAT1 or NAT2, in genotoxicity of nitroarenes and aromatic amines in Salmonella typhimurium NM6001 and NM6002

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Human NAT1 and NAT2 genes were subcloned into pACYC184 vector and the plasmids thus obtained were introduced into Salmonella typhimurium O-acetyltransferase-deficient strain NM6000 (TA1538/1,8-DNP/pSK1002), establishing new strains NM6001 and NM6002, respectively. We compared the sensitivities of these two strains with those of NM6000 towards carcinogenic nitroarenes and aromatic amines in the SOS/umu response. The induction of umuC gene expression by these chemicals in the presence and absence of the S9 fraction was assayed by measuring the cellular β-galactosidase activity expressed by the umuC”lacZ fusion gene in the tester strains. 2-Nitrofluorene and 2-aminofluorene induced umuC gene expression more strongly in the NM6001 strain than in the NM6002 strain. In contrast, induction of umuC gene expression by 1,8-dinitropyrene, 6-aminochrysene and 2-amino-3,5-dimethylimidazo[4,5-f]quinoline was weaker in the NM6001 strain than in the NM6002 strain. 1-Nitropyrene, 2-amino-6-methyl-dipyrido[1,2-a:3′,2′-d]imidazole, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole, 3-amino-1-methyl-5H-pyrido[4,3-b]indole, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 2-amino-3-methyl-9H-pyrido[2,3-b]indole were found to induce umuC gene expression at similar extents in both strains. These results suggest that the newly developed strains can be employed for the studies on mechanisms of genotoxicity of a variety of nitroarenes and aromatic amines, along with the assessment of cancer risk to humans.

Keywords: 1,8-DNP, 1,8-dinitropyrene; 1-NP, 1-nitropyrene; 2-AF, 2-aminofluorene; 2-NF, 2-nitrofluorene; 6-AC, 6-aminochrysene; Glu-P-1, 2-amino-6-methyl-dipyrido[1,2-a:3′,2′-d]imidazole; MeAαC, 2-amino-3-methyl-9H-pyrido[2,3-b]indole; MeIQ, 2-amino-3,5-dimethylimidazo[4,5-f]quinoline; NAT, N-acetyltransferase; O-AT, O-acetyltransferase; PABA, p-aminobenzoic acid; PhIP, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine; SMZ, sulfamethazine; Trp-P-1, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole; Trp-P-2, 3-amino-1-methyl-5H-pyrido[4,3-b]indole

Journal Article.  4221 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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