ABSTRACT
DNA repair-defective alleles of the mei-9, mei-41, mus-104 and mus-101 loci of Drosophila melanogaster were introduced into stocks bearing the UZ and SZ marker sets. Males with the UZ marker set, z 1 (zeste allele) and w +(TE) (genetically unstable white allele presumably caused by a transposable element), or the SZ marker set, z 1 and w +R (semistable white allele caused by partial duplication of the w + locus plus transposon insert), were exposed to EMS at the first instar. After emergence, adult males bearing red spots on lemon-yellow eyes were scored as flies with somatic reversions of w +(TE) or w +R. The relative mutabilities (relative values of reversion frequency at an equal EMS dose) of either w +(TE) or w +R in a repair-proficient strain and in mei-9, mei-41, mus-104 and mus-101 strains were 1:?1.2:0.3:0.3:0.7, despite the fact that w +(TE) reverted two to three times as frequently as w +R under both the repair-proficient and repair-deficient genetic conditions. Similarly, after treatment with MMS, MNNG and ENNG, w +(TE) was somatically more mutable in the mei-9 strain and less mutable in the mei-41 and mus-104 strains than in the repair-proficient strain. From these results, we propose that mutagenic lesions produced in DNA by treatment with these chemicals are converted to mutant DNA sequences via the error-prone repair mechanisms dependent on the products of the genes mei-41 + (mei-41 and mus-104 being alleles of the same locus) and mus-101 +, whereas they are eliminated by mei-9 +-dependent excision repair. In contrast to the approximately linear responses of induced reversions of w +(TE) with ENNG in the repair-proficient, mei-9, and mei-41 strains, seemingly there were dosage insensitive ranges for induced reversion with MNNG in the repair-proficient and mei-41 strains, but not for reversion in the mei-9 strain; w +(TE) in the mus-104 strain was virtually nonmutable with MNNG and ENNG. These results suggest that O 6-methylguanine (O 6MeG) produced in DNA with MNNG, but not O 6-ethylguanine produced with ENNG, is almost completely repaired in a low dose range by constitutive activity of DNA O 6MeG transmethylase. From the distribution of clone sizes of spontaneous revertant spots and other data, we propose that both w +(TE) and w +R have a similar tendency to spontaneously revert more frequently at early rather than at late developmental stages, probably reflecting a common property of their inserted transposons.
Phthalate-Induced Fetal Leydig Cell Dysfunction Mediates Male Reproductive Tract Anomalies
