The nature of X-ray and chemically induced mutations in Drosophila in relation with DNA repair.

ABSTRACT

This paper describes the spectrum of mutations induced by alkylating agents and ionizing radiation in Drosophila. Specifically, the genotoxic profile of the alkylating agents is set against their carcinogenic potency. Alkylating agents that react preferentially with N-atoms in the DNA are relatively poor mutagens, especially so in repair-competent (early) germ cells, and likewise weak carcinogens when compared to those that are more efficient in O-alkylation. Genetic techniques combined with molecular analysis of X-ray and neutron induced mutations show that ionizing radiation induces primarily break-type mutations in a repair proficient background. Both multi-locus deletions as well as small intragenic deletions of only a few base-pairs are observed. The small deletions occur between direct repeats of 2-3 nucleotides, one copy of which is retained in the mutant allele. Possibly, these deletions are the result of repair processes. The effect of changes in DNA-repair (excision repair deficient) is reflected by a "hypermutability" for alkylating agents specifically for N-alkylators, indicating that the normal efficient error-free repair of N-alkylation damage can explain the high exposure doses required for tumor induction in mammals. The frequency of X-ray induced whole-body white mutations, recovered in excision repair deficient Drosophila, is only slightly enhanced, when compared to the repair proficient situation. In contrast, mosaic mutations occur 3-4 times more frequent, indicating that part of the X-ray damage, normally removed by the excision repair process, is not a major impedement during replication.(ABSTRACT TRUNCATED AT 250 WORDS)