Mutagenicity of antiviral substances of nucleobase analogue type in Salmonella typhimurium employing metabolic activation by mouse liver homogenate or cell-free plant extracts

Five nucleobase analogues with antiviral properties were tested for their mutagenic activity in his mutant strains TA 1535, TA 1537, TA 1538, TA98, and TA 100 of S. typhimurium by means of preincubation tests with and without metabolic activation by cell free fractions from mouse liver (S-9) and maize seedlings (S-14). In one bacterial strain 6-azathymine increased the revertant counts in the absence of metabolic activation systems. In the presence of S-9 mix, the same substance became mutagenic for another tester strain. Metabolic activation by S-14 resulted in weak mutagenicity of 5-azadihydrouracil in high concentrations. 6-Azauracil, 5-azauracil, and 5-azadihydro-1,3-diacetyluracil were without mutagenic activity in all Salmonella-strains used. Cyclophosphamide, like other standard promutagens, was shown to become mutagenic in the presence of S-14 plant fraction. Thus S-14 activation system besides the S-9 liver system can be employed in mutagenicity testing with microbial systems.