Some aspects of the detection of potential mutagenic agents in Drosophila

The Drosophila system is a valuable test for detecting and characterizing mutagenic agents. Tester strains are available or can be synthesized for determining almost all types of genetical change ranging from gene mutations to chromosome rearrangements in a great variety of cell types of both sexes. Metabolic activation of all groups of indirect mutagens tested so far (aryldialkyltriazenes, cyclophosphamides, nitrosamines, azo-, hydrazo- and azoxyalkanes, aflatoxins, and polycyclic hydrocarbons; about 35 representatives in all), gives strong although indirect support for the considerable metabolizing ability of Drosophila. This capability would be expected from comprehensive biochemical data on bioactivation of foreign compounds in other insects. From a comparison of which types of genetical change are induced at high, low and threshold concentrations, it appears that lethal tests remain the most reliable method for any screening program. Mutagenic agents such as diethylnitrosamine, hycanthone and certain triazenes, which are highly efficient in the induction of recessive lethals (gene mutations and/or deficiencies), would not have been detected in Drosophila if chromosome breakage were the only indicator for mutagenic activity. Moreover, for several mono- and polyfunctional agents, the lowest dose which is still genetically active was definitely lowest for recessive lethals when compared with dominant lethals, chromosome rearrangements or loss. If a new mutagen is discovered by a screening procedure using Drosophila, an accurate picture of its ability to cause either or both gene mutations and chromosome aberrations can be drawn. Such work will be valuable in helping to clarify similar problems in mammalian systems. For instance, it was important to learn that mutagens of the nitrosamine type apparently fail to produce breakage events in Drosophila. Similarly, three cyclophosphamides appeared not to have chromosome breaking ability. However, from a more detailed study, in which a series of concentrations was used, it became obvious that a penetration effect or, more likely, a rate-limiting factor in bioactivation, was the cause of the negative results obtained with these agents.