Tests for the genotoxicity of m-AMSA, etoposide, teniposide and ellipticine in Neurospora crassa.

The antitumor agents m-AMSA, etoposide, teniposide and ellipticine have been reported to be potent clastogens in mammalian cells but non- or weakly mutagenic in bacteria; these observations have been correlated to the interference of these chemicals with DNA topoisomerase II activity in the former, but not in the latter, organisms. The genotoxicity of these 4 agents was evaluated using ad-3 reverse- and forward-mutation tests in Neurospora crassa. These agents (up to 0.8 mumole/plate) did not cause reversion in conidia of the ad-3A frameshift strains N24 and 12-9-26 using the overlay plate test, as contrasted to the positive control frameshift mutagen ICR-170. Heterokaryon 12 (H-12) of N. crassa permits the recovery of all classes of forward mutation at the ad-3+ region, including multilocus deletions. Using resting conidia of H-12 in a suspension assay, ellipticine was moderately mutagenic but no increase in ad-3 mutants was noted with the other 3 agents at a dose of 100 micrograms/ml. In vegetative cultures of H-12 grown in the presence of these agents, all 4 agents were nonmutagenic at a dose of 100 micrograms/ml. The positive control mutagen ICR-170 was mutagenic in both resting conidia and growing cultures of H-12. A similarity between the topoisomerase II of N. crassa and DNA gyrase of bacteria is suggested.