Specific Genetic Deletions by a Carcinogenic Hydrocarbon in Drosophila

Abstract

THE unequivocal establishment of the somatic mutation theory of cancer requires the demonstration that all carcinogenic agents can induce some viable alterations in the genic DNA. Earlier studies of the mutagenicity of chemical carcinogens (reviewed in ref. 1) yielded positive results for alkylating and nitroso compounds, but not for hydrocarbons and aromatic amines. On the whole, however, these studies were restricted to point mutations: either at few loci in microorganisms or as exemplified by recessive lethals in Drosophila. The possibility therefore remained that mutability with some agents might have occurred at uninvestigated loci, or involved mutational mechanisms unrelated to those resulting in point mutations. Another complication was that carcinogenicity with certain compounds seemed to require previous metabolic activation², which might not occur in some of the genetic test systems used. An extensive investigation was therefore undertaken of the mutational spectra of a wide range of carcinogens—or their active metabolites in Drosophila—and most of the results have recently been published already³. The only genetic aberrations induced by all the compounds tested were the dominant visible mutations resulting in the “Minute” phenotype. These are deletion mutations, hemizygously and homozygously lethal, which have often been located in the heterochromatin^4—6. This suggested that the significant genetic change in carcinogenesis might well be the elimination of specific heterochromatic gene loci, and experiments were designed to test this possibility.