Comparison of the spectra of genetic damage in N4-hydroxycytidine-induced ad-3 mutations between nucleotide excision repair-proficient and -deficient heterokaryons of Neurospora crassa.
A comparison has been made of the mutagenic effects of N4-hydroxycytidine (HC) in the adenine-3 (ad-3) region of two-component heterokaryons of Neurospora crassa: nucleotide excision repair-proficient (uvs-2+/uvs-2+) heterokaryon 12 (H-12) and nucleotide excision repair-deficient (uvs-2/uvs-2) heterokaryon 59 (H-59). HC was found to produce mutations predominantly, if not exclusively, by AT to GC base-pair transitions in Escherichia coli strain K12 by Janion and Glickman (1980, Mutation Res., 72, 43-47) and Sledziewska-Gojska et al. (1992, Mutagenesis, 7, 41-46). The ad-3 forward-mutation, specific-locus assay system permits the recovery of ad-3A and/or ad-3B mutants resulting from gene/point mutation, multiple-locus mutation, and multilocus deletion mutation. Uvs-2, which is homokaryotic in H-59, results in a recovery of HC-induced ad-3 forward mutations at a frequency in H-59 that is comparable to that found in H-12. Genetic analysis of ad-3 mutants recovered from experiments with HC treatment demonstrates that predominantly gene/point mutations were found in both strains: 99.3% (540/544) in H-12, and 97.4% (531/545) in H-59. Genetic analysis of allelic complementation among the ad-3BR mutations demonstrated that HC induced the highest percentage of complementing mutants ever found with base analogs both in H-12 (99.7% [328/329]) and H-59 (91.2% [290/318]). As a result of these findings, the majority of HC-induced ad-3 mutations are postulated to have resulted from missense mutations. Thus, we conclude that the results in Neurospora are consistent with the observations in E. coli strain K-12, where HC induces predominantly AT to GC base-pair transitions.
de Serres
F J
FJ
Center for Life Sciences and Toxicology, Research Triangle Institute, NC 27709.
Brockman
H E
HE
D000225:Adenine; D000483:Alleles; D003562:Cytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004249:DNA Damage; D004260:DNA Repair; D016206:Databases, Bibliographic; D004926:Escherichia coli / Q000235:genetics; D005816:Genetic Complementation Test; D005838:Genotype; D009153:Mutagens / Q000494:pharmacology*; D009154:Mutation; D009492:Neurospora crassa / Q000187:drug effects / Q000235:genetics*
D009153:Mutagens; D003562:Cytidine; C010737:N(4)-hydroxycytidine; D000225:Adenine