Dependence on Salmonella typhimurium enzymes of mutagenicities of nitrobenzene and its derivatives in the presence of rat-liver S9 and norharman.
Dependence on S. typhimurium enzymes of mutagenicities of nitrobenzene (NB) and o-, p-chloronitrobenzenes (o-, p-CNBs), which are only mutagenic in the presence of S9 and norharman (NOH), was investigated using a nitroreductase-deficient strain TA98NR and an esterifying enzyme-deficient strain TA98/1,8-DNP6. NB exhibited mutagenicity towards TA98 but did not towards TA98NR strain in spite of the presence of S9 in the assay system. The mutagenicity of o-CNB towards TA98NR was significantly lower than that of o-CNB towards TA98. In contrast to NB and o-CNB, synthesized phenylhydroxylamine (PHA) and o-chlorophenylhydroxylamine (o-CPHA) exhibited approximately the same mutagenicity towards both tester strains. These results indicate that the nitroreduction required for the appearance of mutagenicity of the nitrobenzene derivatives in the presence of S9 and NOH is dependent on the nitroreductase of the tester strain. In addition, the mutagenicities of PHA and p-CPHA were significantly higher towards TA98/1,8-DNP6 than towards TA98, suggesting that the esterification of their hydroxylamines produced inactivation rather than activation. From these results, it was concluded that S9 and NOH play a role in metabolic activation other than the reduction of the nitro group to hydroxylamine and subsequent esterification for the mutagenesis of NB and its derivatives.
Suzuki
J
J
Takahashi
N
N
Kobayashi
Y
Y
Miyamae
R
R
Ohsawa
M
M
Suzuki
S
S
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology*; D001711:Biotransformation; D002243:Carbolines; D006247:Harmine / Q000031:analogs & derivatives / Q000494:pharmacology*; D006898:Hydroxylamines / Q000494:pharmacology; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D009152:Mutagenicity Tests; D009578:Nitrobenzenes / Q000494:pharmacology*; D009601:Nitroreductases / Q000502:physiology*; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects / Q000201:enzymology*
D000470:Alkaloids; D001426:Bacterial Proteins; D002243:Carbolines; D006898:Hydroxylamines; D009578:Nitrobenzenes; D006247:Harmine; C010262:norharman; D010088:Oxidoreductases; D009601:Nitroreductases