Cytogenetic Analysis of the Action of Carcinogens and Tumor Inhibitors in Drosophila Melanogaster. VIII. Selective Mutagenic Activity of S-2-Chloroethylcysteine on the Spermatogonial Stages.

HE greatest majority of the physical and chemical mutagens so far investiTgated in Drosophila proved to be far more active on the postmeiotic stages of spermatogenesis than on the premeiotic cells (X-radiation: LUNING 1952; various alkylating compounds: BIRD and FAHMY 1953; FAHMY and FAHMY 1954, 1955, 1957a, 1958a,b, 1960a). The mustard derivatives of naturally occurring amino acids deviated from this predominant pattern in so far as they proved to be mutagenetically active on all stages of the germ line, particularly the gonia ( FAHMY and FAHMY 1960a). This selectivity for the anabolically active cells was attributed to “metabolic transport”, whereby the amino acid mutagenic molecule could be conveyed through the cytosome to sites of nucleoprotein synthesis during chromosome replication. As a further test of this hypothesis, the mutageriicity of a monofunctional mustard derivative of a naturally occurring amino acid, viz. S-2-chloroethylcysteine, was analyzed. It was thought possible that in a molecule with a single alkylating group (the chloroethyl radical), the relative r6le of the alkylating to the prosthetic moiety in mutagenesis may be weighted in favor of the latter, thus exaggerating selectivity of action on the metabolically active cells. The mutagenic cell-stage response of S-2-chlorcethylcysteine is also of interest in relation to the mode of action of 2-chloroethyl methanesulphonate (FAHMY and FAHMY 1956a). The activity of this sulphonate on spermatogonia, in contrast to several other mesyloxy-esters, suggested the production in viuo of a secondary mutagen, probably an amino acid mustard (FAHMY and FAHMY 1957a). Biochemical evidence (ROBERTS and WARWICK 1957, 1958) indicated that the secondary mutagen is likely to be S-2-chloroethylcysteine. The mutagenic properties of this compound were accordingly investigated, with a view to the further elucidation of the suggested in uiuo conversion of 2-chlbroethyl methanesulphonate.