Analysis of mutational specificity induced by heterocyclic amines in the lacZ gene of Escherichia coli.
Mutational spectra induced by different heterocyclic amines were characterized and compared with those obtained from diethylnitrosamine and N-methyl-N-nitrosourea. Mutation classes were identified by means of a series of mutant lacZ genes in F' episomes in Escherichia coli engineered to detect specifically each of two transitions, four transversions and five kinds of frameshift events. More than 99.5% of the mutations induced by heterocyclic amines were frameshift mutations. -2(C.G-G.C) frameshifts were favored over other types, such as +1(G.C), -1(G.C), +1(A.T) and -1(A.T), except when 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) was administered. -1(G.C) and +1(G.C) frameshifts predominate following Trp-P-1 treatment. A small number of G.C-->T.A transversions were induced by the treatment with 2-amino-3,4-dimethylimidazo[4,5-f]quinoline as well as with several other heterocyclic amines examined. Since G.C-->T.A transversions, but not frameshift mutations, are reported to play a role in heterocyclic amine-induced activation of the c-Ha-ras protooncogene or inactivation of the p53 tumor suppressor gene, the low level of base substitutions, particularly G.C-->T.A transversions, may represent a partial explanation for the relatively modest carcinogenic activity of heterocyclic amines, despite their extraordinarily strong mutagenicity in the Salmonella mutation assay.
Institute of Environmental Toxicology, Tokyo, Japan.
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Watanabe
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Ohta
D000588:Amines / Q000737:chemistry / Q000494:pharmacology*; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004052:Diethylnitrosamine / Q000494:pharmacology; D004926:Escherichia coli / Q000235:genetics*; D016368:Frameshift Mutation; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000494:pharmacology*; D007763:Lac Operon / Q000187:drug effects*; D008770:Methylnitrosourea / Q000494:pharmacology; D008969:Molecular Sequence Data; D009154:Mutation
D000588:Amines; D006571:Heterocyclic Compounds; D004052:Diethylnitrosamine; D008770:Methylnitrosourea