Comparison of the spectra of genetic damage in formaldehyde-induced ad-3 mutations between DNA repair-proficient and -deficient heterokaryons of Neurospora crassa.
The mutagenic effects of formaldehyde (FA) have been compared in DNA repair-proficient (heterokaryon 12) and DNA repair-deficient (heterokaryon 59) two-component heterokaryons of Neurospora crassa. The data from forward-mutation experiments were used to compare the spectra of FA-induced specific-locus mutations at two closely linked loci in the adenine-3 (ad-3) region and on the FA-induced inactivation of heterokaryotic conidia. Previous studies have demonstrated that specific-locus mutations at these two loci result from five major genotypic classes, namely two classes of gene/point mutations (ad-3A(R) and ad-3B(R)), and three classes of multilocus deletion mutations ([ad-3A](IR), [ad-3B](IR), and [ad-3A ad-3B](IR)). Genetic analysis of ad-3 mutants recovered from both heterokaryons after FA treatment demonstrates that predominantly gene/point mutations were found in H-12 (93.2% ad-3(R), 6.8% [ad-3](IR)) and a significantly higher frequency of multilocus deletion mutations in H-59 (62.8% ad-3(R), 37.0% [ad-3](IR)). The data from our experiments with FA on H-12 demonstrate and confirm the data from other assays that FA is a weak mutagen in this DNA repair-proficient strain. However, the data from our experiments with the DNA repair-deficient strain H-59 demonstrate that comparable concentrations of FA cause more pronounced inactivation of heterokaryotic conidia and, at the highest concentration tested, about a 35-fold higher frequency of ad-3 mutations. In addition, FA induced a 5.4-fold higher frequency of ad-3 mutations resulting from multilocus deletion mutation in H-59 than in H-12. Based on our earlier studies with X-ray-induced multilocus deletion mutations, it is this class of FA-induced ad-3 mutations that might be most expected to show deleterious heterozygous effects. The implications of the present data base from our experiments with Neurospora are that the mutagenic (and possibly the carcinogenic) effect of FA exposure might well vary in different human population subgroups.
de Serres
F J
FJ
Mammalian Mutagenesis Group, Laboratory of Toxicology, Systems Toxicology Branch, Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27703-27709, USA. deserres@niehs.nih.gov
Brockman
H E
HE
D000225:Adenine / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics; D005557:Formaldehyde / Q000633:toxicity*; D005800:Genes, Fungal; D005838:Genotype; D006801:Humans; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D009492:Neurospora crassa / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism
D009153:Mutagens; D005557:Formaldehyde; D000225:Adenine