CYTOGENETIC ANALYSIS OF THE ACTION OF CARCINOGENS AND TUMOUR INHIBITORS IN DROSOPHILA MELANOGASTER. IX. THE CELL-STAGE RESPONSE OF THE MALE GERM LINE TO THE MESYLOXY ESTERS

O G Fahmy, Myrtle J Fahmy
1961 Genetics  
STUDY of the mutagenicity of a series of nitrogen mustards has shown that A the structure of the nonalkylating (or prosthetic) moiety of the molecule has some bearing on biological activity. The same molar dose of difunctional compounds with roughly equal chemical reactivity, but with different prosthetic groups, induced in the sperm significantly different mutation rates (FAHMY and FAHMY 1960a). The prosthetic group of the mustard molecule also played a major role in the determination of the
more » ... ttern of cell-stage response during spermatogenesis. The relative mutation rate of the various stages of the male germ line was markedly different according to whether the mustard was a derivative of an amino acid, a carboxylic acid, or an amine (FAHMY and FAHMY 1960b). Another series of the alkylating agents which proved to be effective mutagens on the testis of adult Drosophila, is the mesyloxy esters (BIRD 1951; FAHMY and FAHMY 1956a). The mutagenic cell-stage response during spermatogenesis under a homologous series of monofunctional methanesulphonates was investigated and proved to be fairly consistent and characteristic: the spermatogonial stages were refractory, while the postspermatogonial stages were responsive, 'with maximal effect on mature sperm (FAHMY and FAHMY 1957). The question then arose as to whether this pattern of cell-stage response is typical of the mesyloxy esters. The analysis of the cell-stage effect was accordingly extended to several other sulphonates with a view to the elucidation of the consequences of changes in the mutagenic molecule, both as regards the number of the functional groups (the mesyloxy radicals) and the structure of the prosthetic moiety. The compounds analysed are all esters of methanesulphonic acid, and were synthesized in the chemistry department in relation to cancer chemotherapy (HADDOW 1955) . From the chemical point of view they are either mono-or difunctional as regards the alkylating groups (the mesyloxy radicals) but with different prosthetic moieties; the latter varied as regards chain length, valency unsaturation, steric configuration, and degree of hydroxylation (substitution by
doi:10.1093/genetics/46.4.361 fatcat:m3apvv5llvc3zdixfurxgv3oeu