NITROREDUCTASE INDEPENDENT MUTAGENICITY OF 1-HALOGENATED-2,4-DINITROBENZENES

The 1-halogen substituted 2,4-dinitrobenzenes have been found to be mu tagenic in Salmonella TA98 with an activity order of l-fluoro > l-chlo ro > I-bromo > I-iodo. This specific activity was not lowered in the n itroreductase deficient strain TA98NR and O-acetyltransferase deficien t strain TA98/1,8-DNP6, indicating that the mutagenicity of these comp ounds is not dependent upon -NO2 reduction to -NHOH and its subsequent esterification. The activity was, rather, higher in the former and re mained almost equal in the latter strain compared to TA98, suggesting these compounds to react directly with bacterial DNA. Further, the rea ction of these halodinitrobenzenes with methionine, at physiological p H, resulting in the formation of 1-S-methyldinitrobenzene showed that these compounds have the ability to attack DNA directly through nucleo philic substitution of the halogen atom and the role of the bacterial nitroreductases for production of mutagenic lesions was not considered . It was, further, proposed that these compounds interact with DNA thr ough SNAr mechanism instead of S(N)2 cited in literature. (C) 1997 Els evier Science B.V.