Comparative mutagenicity of plant‐activated aromatic amines using salmonella strains with different acetyltransferase activities

Plant systems can activate aromatic amines into mutagens. In the plant cell/microbe coincubation assay, we earlier demonstrated that 2‐aminofluorene and m‐phenylenediamine were activated by plant cells into mutagens with reversion at the hisD3052 allele in Salmonella typhimurium strain TA98 as the genetic endpoint. New derivatives have been developed which possess elevated levels of acetyl‐CoA:N‐hydroxyarylamine O‐acetyltransferase which are very sensitive to N‐hydroxylated amines [Watanabe et al., 1990: Mutat Res 234:337‐348]. The objectives of this research were to examine Salmonella strains with different acetyltransferase activities in the plant cell/microbe coincubation assay with a series of structurally related aromatic amines. The hypothesis tested was whether and to what degree a plant‐activated metabolite of these aromatic amines could serve as a substrate for bacterial O‐acetyltransferase and induce mutation in Salmonella. Every aromatic amine examined was activated by plant cells with YG1024 (the strain with elevated O‐acetyltransferase activity) as the genetic indicator organism. The rank order of the mutagenic responses of YG1024 to the plant‐activated aromatic amines was 2‐aminofluorene >benzidine > m‐phenylenediamine > 4‐aminobiphenyl > 2,4‐diaminotoluene > 2‐naphthylamine. This rank order was expressed by TA98 but to a much lower degree. There was a very slight mutagenic response observed in TA98/1,8‐DNP6 (a strain lacking O‐acetyltransferase activity) with the plant‐activated metabolites of benzidine and 4‐aminobiphenyl. We conclude that the plant‐activated aromatic amines are substrates for bacterial O‐acetyltransferases. © 1994 Wiley‐Liss, Inc.

[1]  M. Plewa,et al.  Biochemical and mutagenic characterization of plant‐activated aromatic amines , 1993 .

[2]  M. Plewa,et al.  Characterization of stable high molecular weight mutagenic product(s) of plant-activated m-phenylenediamine. , 1993, Mutation research.

[3]  M A Butler,et al.  Polymorphisms for aromatic amine metabolism in humans: relevance for human carcinogenesis. , 1992, Environmental health perspectives.

[4]  Josephy Pd,et al.  Salmonella typhimurium strains expressing human arylamine N-acetyltransferases: metabolism and mutagenic activation of aromatic amines. , 1992 .

[5]  T. Sofuni,et al.  Involvement of Cys69 residue in the catalytic mechanism of N-hydroxyarylamine O-acetyltransferase of Salmonella typhimurium. Sequence similarity at the amino acid level suggests a common catalytic mechanism of acetyltransferase for S. typhimurium and higher organisms. , 1992, The Journal of biological chemistry.

[6]  D. Grant,et al.  Site-directed mutagenesis of recombinant human arylamine N-acetyltransferase expressed in Escherichia coli. Evidence for direct involvement of Cys68 in the catalytic mechanism of polymorphic human NAT2. , 1992, The Journal of biological chemistry.

[7]  M. Plewa,et al.  Diethyldithiocarbamate suppresses the plant activation of aromatic amines into mutagens by inhibiting tobacco cell peroxidase. , 1991, Mutation research.

[8]  H. Matthews,et al.  Evidence for an acetoxyarylamine as the ultimate mutagenic reactive intermediate of the carcinogenic aromatic amine 2,4-diaminotoluene. , 1990, Mutation research.

[9]  M Ishidate,et al.  Sensitive method for the detection of mutagenic nitroarenes and aromatic amines: new derivatives of Salmonella typhimurium tester strains possessing elevated O-acetyltransferase levels. , 1990, Mutation research.

[10]  M. Plewa,et al.  Effects of specific monooxygenase and oxidase inhibitors on the activation of 2-aminofluorene by plant cells. , 1989, Mutation research.

[11]  T. Eling,et al.  Prostaglandin H synthase-dependent mutagenic activation of benzidine in a Salmonella typhimurium Ames tester strain possessing elevated N-acetyltransferase levels. , 1989, Cancer research.

[12]  H. Sandermann,et al.  Mutagenic activation of xenobiotics by plant enzymes. , 1988, Mutation research.

[13]  M. Plewa,et al.  The plant cell/microbe coincubation assay for the analysis of plant-activated promutagens. , 1988, Mutation research.

[14]  T. Kamataki,et al.  Metabolic activation of mutagenic N-hydroxyarylamines by O-acetyltransferase in Salmonella typhimurium TA98. , 1985, Archives of biochemistry and biophysics.

[15]  T. Kamataki,et al.  Mechanism of activation of proximate mutagens in Ames' tester strains: the acetyl-CoA dependent enzyme in Salmonella typhimurium TA98 deficient in TA98/1,8-DNP6 catalyzes DNA-binding as the cause of mutagenicity. , 1983, Biochemical and biophysical research communications.

[16]  H. Rosenkranz,et al.  The basis of the insensitivity of Salmonella typhimurium strain TA98/1,8-DNP6 to the mutagenic action of nitroarenes. , 1983, Mutation research.

[17]  M. Plewa,et al.  Activation of 2-aminofluorene by cultured plant cells. , 1983, Science.

[18]  B. Ames,et al.  Revised methods for the Salmonella mutagenicity test. , 1983, Mutation research.

[19]  F. Skoog,et al.  A revised medium for rapid growth and bio assays with tobacco tissue cultures , 1962 .

[20]  D. Grant,et al.  Salmonella typhimurium strains expressing human arylamine N-acetyltransferases: metabolism and mutagenic activation of aromatic amines. , 1992, Cancer research.

[21]  M. Ishidate,et al.  Mutagenicity of 30 chemicals in Salmonella typhimurium strains possessing different nitroreductase or O-acetyltransferase activities. , 1991, Mutation research.

[22]  M. Plewa,et al.  The biochemical mechanisms of the plant activation of promutagenic aromatic amines , 1990, Environmental and molecular mutagenesis.

[23]  Louis J. Romano,et al.  Carcinogenic and mutagenic responses to aromatic amines and nitroarenes : proceedings of the Third International Conference on Carcinogenic and Mutagenic N-Substituted Aryl Compounds, held April 25-28, 1987, in Dearborn Michigan , 1988 .

[24]  M. Plewa,et al.  Plant activation of m‐phenylenediamine by tobacco, cotton, and carrot cell suspension cultures , 1987, Environmental and molecular mutagenesis.

[25]  W. Weber.  The acetylator genes and drug response , 1987 .