Cytogenetic analysis of the action of carcinogens and tumour inhibitors inDrosophila melanogasterI. 1:2, 3:4-diepoxybutane

Abstract

This analysis is part of an investigation designed for the elucidation of the correlation between mutagenesis and carcinogenesis. Diepoxybutane was found to be a strong mutagen when injected into the haemocoel of adultDrosophilamales, producing lethal, semi-lethal and ‘visible’ mutations. One of the ‘visible’ mutations produced resulted in the appearance of neoplastic melanotic ‘tumours’ in the offspring of the treated flies. This is most significant in relation to the mutation theory of cancer causation. The successive stages of the male germ line manifest a varied susceptibility to mutagenic action, there being a certain stage among the earlier germ cells which is the most sensitive. The proportion of major structural rearrangements among the sex-linked recessive lethals produced by chemical agents (diepoxybutane and mustard gas) is far lower than that produced by mutagenically equivalent doses of X-rays. Small deficiencies, on the other hand, are twice as frequent among diepoxybutane lethals as among the same type of mutation induced by mustard gas or X -rays. The quality of the bands involved in the deficiencies is also different, diepoxybutane affecting the darker bands of the salivary glandX-chromosome preferentially, mustard gas the lighter ones. This might indicate that diepoxybutane has a preferential action on the gene loci with a higher charge of nucleic acid. A ‘coarse’ specificity for chromosome segments, however, does not seem to occur. The distributions of recessive lethals and loci of damage, induced by the diepoxide and mustard gas in the successive segments of theX-chromosome, are not significantly different. Mosaics for visible mutations and chromosomal changes occur more frequently after treatment with chemical mutagens than after X-radiation. This mosaicism has been explained on the basis of the multiple-strand structure of the mitotic chromosome and partial damage to some of its subunits.