0000000000596165
AUTHOR
Patrizia Hrelia
Analysis of metabolism and genotoxicity of 5-nitro-3-thiophenecarboxanilides in bacterial, mammalian and human cells
5-nitro-3-thiophenecarboxanilide (NTCA3) was clearly mutagenic in Salmonella typhimurium strains TA98, YG1021 (the strain with elevated nitroreductase) and YG1024 (the strain with elevated O-acetyltransferase) and only slightly mutagenic at the gpt locus in AS52 cells. Clastogenic activity in human lymphocytes was dependent on the length of exposure : detectable chromosome aberrations were observed following a 24 h treatment period, but not after 3 h exposure. S9 increased genotoxicity in both mammalian cells and human lymphocytes. Metabolites formed by incubation of NTCA3 with the different cell systems were examined. A time-course study in cell whole extracts showed that bacterial and mam…
Influence of nitroreductase and O-acetyltransferase on the mutagenicity of substituted nitrobenzothiophenamines in Salmonella typhimurium.
The mutagenic activity of 17 substituted (aryl)(2-nitrobenzo[b]thiophen-3yl)amines has been evaluated in the Ames test with different isogenic strains of Salmonella typhimurium, that varied in their expression of nitroreductase and O-acetyltransferase. Active derivatives induced frameshift mutations in TA98 strain, and differences in the chemical structure resulted in up to 15-fold changes in mutagenic activity. The non-mutagenic compounds are the unsubstituted parent compound and derivatives with para-chloro, para-fluoro, para-diethylamino, meta-bromo and para-dimethylamino groups. They do not show any activity even in strains with higher level of nitroreductase or O-acetyltransferase. The…
Mechanism of genotoxicity and electron density distribution by NMR of 5-nitro-3-thiophenecarboxamides, a novel group of direct-acting mutagens in Salmonella typhimurium.
Abstract The mutagenic activity of 23 5-nitro-3-thiophenecarboxanilides and of 5-nitro-3-thiophenecarboxamide, the prototype, (NTCAs) have been evaluated in the Ames test on Salmonella typhimurium strains TA100 ad TA98 with and without metabolic activation. Effects of different substituents (electron-donating and electron-withdrawing) were studied to evaluate structural features that affect the metabolism and the bacterial mutagenic potency. All the derivatives were direct-acting mutagens, the mutagenic potency ranging from 0.7 to 142 revertants (rev.)/nmol in TA100 and from 0.09 to 68 rev./nmol in TA98 strain. Results obtained with strains TA98NR and TA98/1,8-DNP 6 indicated that the mutag…