ANALYSIS OF MITOTIC RECOMBINATION INDUCED BY SEVERAL MONOFUNCTIONAL AND BIFUNCTIONAL ALKYLATING-AGENTS IN THE DROSOPHILA WING-SPOT TEST

Mitotic recombination induced by six alkylating agents has been studie d in the wing-spot test of Drosophila melanogaster. The model mutagens chosen have different modes of action at the DNA level. These are: th e direct-acting small alkylating agent methylmethanesulfonate (MMS), t he small promutagens N-dimethylnitrosamine (DMN), and N-diethylnitrosa mine (DEN), the bifunctional cross-linking alkylating agents mitomycin C (MMC), chlorambucil (CLA) and monocrotaline (MCT). Flies of the sta ndard cross (flr(3)/TM3, Bd(S) females and mwh males) were used to pro duce the larvae to be treated. Three-day-old Drosophila larvae were ex posed by chronic feeding for 48 h to three different concentrations of all six alkylating agents. Acute feeding for only 2 h was used in add ition with DEN and MMC. Wings of the marker-heterozygous (mvh+/+flr(3) ) as well as of the balancer-heterozygous (mwh+/TM3, Bd(S)) progeny we re analysed. The ranking of the compounds with respect to their genoto xic potency, based on mwh clone formation frequency in marker-heterozy gous wings, was: MMS > MMC > DMN > CLA similar to MCT > DEN. The ranki ng with respect to the induction of twin spots, which are produced by mitotic recombination exclusively, was: MMS > DMN > MMC > MCT > CLA > DEN. The quantitative determination of recombinagenic activity, based on mwh clone formation frequencies obtained in both types of wings, ga ve the following values: MMS, 93%; MCT, 87%; CLA, 80%; MMC, 73%; DMN, 67%; DEN, 22%. A clear relationship exists between the extent of N-alk ylation of DNA and the efficiency of the monofunctional agents MMS and DMN as well of the bifunctional agents MCT, CLA and MMC to induce mit otic recombination. This contrasts with the ethylation of base oxygen atoms and the resulting lower efficiency of DEN to produce mitotic rec ombination.