HEXAMETHYLMELAMINE IS A POTENT INDUCER OF DELETIONS IN MALE GERM-CELLS OF DROSOPHILA-MELANOGASTER

Chemotherapy-related second tumors constitute a matter of concern in c ancer treatment. Therefore, it is of great interest to elucidate the m echanisms by which cytostatic drugs exert their mutagenic and/or carci nogenic activity besides the anticancer effect and the possible relati onship among them, A useful and informative approach to this problem i s the analysis of the mutation spectra induced by these drugs in eukar yotic organisms, Sequence analysis of the mutations induced by hexamet hylmelamine, a crosslinking agent extensively used in the treatment of ovarian cancer, in male germ cells of Drosophila was conducted using the v locus as reporter gene, Both intra-locus and multi-locus deletio ns were induced whereas base changes were almost absent, Thus, it is p roposed that deletions are likely to be involved in the generation of second malignancies in hexamethylmelamine-treated patients. It has to be stressed that systems, such as v, capable of efficiently recovering mutations caused by big losses of DNA, should be used for the study o f mutational spectra induced by cross-linking agents.