Somatic cell mutagenesis in Drosophila: recovery of genetic damage in relation to the types of DNA lesions induced in mutationally unstable and stable X-chromosomes

Abstract

This paper reports the results of a study on the genotoxic activities of 12 mutagens and clastogens of widely differing mode of action in somatic cells in vivo, i.e., in the eye primordia of Drosophila larvae. After emergence, adult flies were monitored for aberrantly colored sectors in the compound eyes of the following genotypes: UZ males and females ( zeste) carrying a genetically unstable transposable element, SZ males and females ( zeste) carrying a partial duplication of the w + locus plus a transposon insert, white-cora/white ( w co w ) females, w +/ w females and w + males. The UZ and SZ marker sets make it possible to monitor shifts from zeste to red (scored as mosaic red spots, RS) and for loss of the white locus (light spots, LS). w co w + females were scored for mosaic twin spots (TS) and LS, w + genotypes for just LS. The genotoxins analyzed were methyl methanesulfonate (MMS), dimethyl sulfate (DMS) and ethylnitrosourea (ENU) (alkylating), adriamycin (AM0 and daunomycin (DM) (intercalating), Trenimon, Thio-TEPA and cisplatin (DDP) (cross-linking), bleomycin (strand-breaking),7,12-dimethylbenz[ a]-anthracene (DMBA) and 9,10-dimethylanthracene (DA) (bulky monoadducts) and cytosine arabinofuranoside (inhibition of DNA synthesis). The relative mutabilities with frequencies of mosaic light spots (LS) in w + w ♀ as the standard (relative mutability = 1) vs. genotypes UZ (RS in ♂) vs. SZ (RS in ♂) vs. w + (LS in ♂) were 1:0.6:0.2:0.3 for MMS, 1:0.09:0.05:0.7 for DDP, and 1:1.6:0.2:1.0 for ENU. ENU showed exceptional behavior in that it was the only compound for which mutational response, measured by the induction of red spots, was highest with the UZ marker set. Occurrence of large light spots (LS) in male but not in female genotypes was negatively correlated with efficiently of agents for chromosomal damage, suggesting that in the hemizygous condition, as in males, selection of damaged cells and mitotic delay may have played a significant role. In general, the results indicate that there is no association between the ability of an agent to act as a clastogen and the recovery of aberrant (red spots) sectors in either the UZ or the SZ strain, and of single light spots (LS) in w +, UZ and SZ males. The possibility is considered that the process causing the genetic instability in the UZ strain is under genetic control, and that strong point mutagens such as ENU through efficient gene mutation induction can interfere with it.