Mutagenic activity and specificity of hydrogen peroxide in the ad-3 forward-mutation test in two-component heterokaryons of Neurospora crassa.

In the ad-3 forward-mutation test, hydrogen peroxide was at best a weak mutagen in nongrowing conidia from a DNA repair-proficient heterokaryon (H-12, uvs-2+/uvs-2+) but was a moderate mutagen in nongrowing conidia from a DNA-repair-deficient heterokaryon (H-59, uvs-2/uvs-2) over a narrow range of high concentrations. H-59 also was more sensitive than H-12 to the killing activity of hydrogen peroxide at high concentrations. Thus, a DNA-repair pathway, of which the gene product of the uvs-2+ allele is a part, appears to be involved in the repair of hydrogen peroxide-induced DNA lesions at low survival in these strains. There was slightly, but significantly, more killing by hydrogen peroxide of nongrowing conidia from H-12 and H-59 in the presence of O2 than in the absence of O2 (presence of N2). Thus, the killing activity of hydrogen peroxide was enhanced by O2. The Mutational Spectra of hydrogen peroxide-induced ad-3 mutants shows that hydrogen peroxide induced mainly gene/point mutations but also some multilocus deletion mutations in H-12 and H-59. Multiple-locus mutations occurred only in H-59, but the frequency was very low. The frequencies of the 3 kinds of intracistronic complementation pattern among ad-3BR mutants (gene/point mutations) suggest that hydrogen peroxide induced both base-pair substitutions and frameshift mutations in both strains.