Cytogenetic analysis of the action of carcinogens and tumour inhibitors in Drosophila melanogaster. XI. Mutagenic efficiency of the mesyloxy esters on the sperm in relation to molecular structure.
Cytogenetic analysis of the action of carcinogens and tumour inhibitors in Drosophila melanogaster. XI. Mutagenic efficiency of the mesyloxy esters on the sperm in relation to molecular structure.
复制标题
黑腹果蝇致癌物和肿瘤抑制剂作用的细胞遗传学分析。
作者：
O. G. Fahmy;M. J. Fahmy
HADDOW和TIMMIS（1953）讨论了导致发现具有生物活性的甲磺酰氧基酯的化学原理。对该系列化合物的后续研究充分证明了其对果蝇成虫睾丸的致突变性（BIRD 1951; FAHMY和FAHMY 1956、1957、1959、1961 a、B）。该系列的一个特定成员，即甲烷磺酸乙酯，被证明是大麦（HESLOT和FERRARY 1958; HESLOT、FERRARY、LEVY和MOUARD 1959; EHRENBERG 1960）以及脉孢菌属（datafGAARD 1957）、细菌（LOVELESS和HOWARTH 1959）和噬菌体（LOVELESS 1959）中的有效诱变剂。甲磺酰氧基酯也被证明是肿瘤生长的活性细胞抑制剂（HADDOW 1955）;一种化合物“Myllethyl”（1：4-二甲磺酰氧基丁烷）现已成为治疗慢性髓性白血病的有用药物（GALTON 1956）。甲磺酰氧基酯与其他烷基化化合物（多胺、环氧化物和乙烯亚胺）一样，其生物活性归因于它们具有化学反应性亲电基团，这些亲电基团可以在活组织中出现的温和条件下烷基化细胞的亲核中心（Ross 1953）。然而，有可能证明，诱变性不仅受到烷基化基团（氯乙基氨基自由基）反应性的影响，而且还受到非烷基化或“假体”部分（分子的剩余部分）的分子构型的影响。根据芥子气的非烷基化部分是氨基酸、羧酸还是胺，雄性生殖系各阶段的相对致突变反应不同（FAHMY和FAHMY 1960 b）。此外，可以证明，具有大致相同化学反应性的不同分子量的精子的致突变性存在显著差异，但具有不同的“假体”基团（FAHMY和FAHMY 1960 a）。还研究了“假体”部分在诱变中的作用。甲磺酰氧基酯。这一系列化合物的非烷基化部分的分子结构变化显著，但在精子发生过程中仍具有基本相同的致突变性模式（FAHMY和FAHMY 1961 a）。T H E
HE chemical rationale that led to the discovery of the biologically active mesyloxy esters has been discussed by HADDOW and TIMMIS (1953). Subsequent work on compounds of this series gave ample evidence for their mutagenicity on the testes of adult Drosophila (BIRD 1951; FAHMY and FAHMY 1956, 1957, 1959, 1961a,b). A particular member of the series, viz. ethyl methanesulphonate, proved to be an effective mutagen in barley (HESLOT and FERRARY 1958; HESLOT, FERRARY, LEVY and MOUARD 1959; EHRENBERG 1960) as well as in Neurospora ( WESTERGAARD 1957), bacteria (LOVELESS and HOWARTH 1959) and bacteriophage (LOVELESS 1959). The mesyloxy esters were also shown to be active cytostatic agents on neoplastic growth (HADDOW 1955) ; one compound “Myleran” (1 : 4-dimethanesulphonoxybutane) has now become a useful drug in the treatment of chronic myeloid leukaemia (GALTON 1956). The mesyloxy esters, like the rest of the alkylating compounds (mustards, epoxides and ethyleneimines) owe their biological activity to the fact that they possess chemically reactive electrophilic groups which can alkylate the nucleophilic centres of the cell under the mild conditions that occur in living tissues (Ross 1953). It was possible to demonstrate, however, that mutagenicity under the mustards is influenced not only by the reactivity of the alkylating groups, (the chloroethylamino radicals) but also by the molecular configuration of the nonalkylating or ‘prosthetic’, moiety (the residual part of the molecule). The relative mutagenic response of the stages of the male germ line differed according to whether the nonalkylating moiety of the mustard was an amino acid, a carboxylic acid, or an amine (FAHMY and FAHMY 1960b). Furthermore it was possible to show that significant differences occurred in the mutagenicity on the sperm with different mustards of roughly the same chemical reactivity, but with various ‘prosthetic’ groups (FAHMY and FAHMY 1960a). The role of the ‘prosthetic’ moiety in mutagenesis was also investigated for the. mesyloxy esters. Compounds of this series which vaned markedly as regards the molecular structure of the nonalkylating moiety, still gave essentially the same mutagenicity pattern during spermatogenesis ( FAHMY and FAHMY 1961 a). T h e