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Evaluation of the mutagenic and genotoxic activities of 48 nitroimidazoles and related imidazole derivatives by the Ames test and the SOS Chromotest
Author(s) -
De Méo M.,
Vanelle P.,
Bernadini E.,
Laget M.,
Maldonado J.,
Jentzer O.,
Crozet M. P.,
Duménil G.
Publication year - 1992
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.2850190212
Subject(s) - ames test , imidazole , genotoxicity , chemistry , mutagen , sos response , nitrofuran , salmonella , stereochemistry , toxicology , escherichia coli , carcinogen , organic chemistry , biochemistry , toxicity , biology , bacteria , genetics , gene
The mutagenic and genotoxic activities of 48 nitroimidazoles and related imidazole derivatives have been evaluated by using modified versions of the Ames test and the SOS Chromotest. Salmonella typhimurium tester strain TA 100 was used with and without metabolic activation in the Ames test and Escherichia coli tester Strain PQ 37 was used with and without metabolic activation in the SOS Chromotest. Including metronidazole and dimetridazole, 45 derivatives were mutagenic and genotoxic. The mutagenic potencies (MP) ranged from 0.127 to 53,717 revertants/nmol while the SOS induction powers (SOSIP) ranged from 0.00131 to 107 IF/nmol. The overall correlation between MP and SOSIP was r = 0.845 (n = 84) as calculated by linear regression analysis. A higher correlation was observed between MP and SOSIP without the S9 mix than with it. Among the imidazole derivatives, the 5‐nitroimidazoles with a lactam ring at the 2‐position showed the highest MP and SOSIP. The presence of a nitro group at the 5‐position was critical for the mutagenicity and the genotoxicity of the derivatives. Substituents at the 1‐ and 2‐positions were also found to modulate these activities.