Biotransformation of Xenobiotics in Drosophila melanogaster and Its Relevance for Mutagenicity Testing

Abstract

Biotransformation of lipophilic xenobiotics may lead to formation of reactive intermediates which can give rise to irreversible toxic events such as carcinogenesis, mutagenesis, teratogenesis, and tissue necrosis. In recent years considerable attention has been paid to the problem of testing for these effects. Short-term mutagenicity tests have been shown to have value for predicting the occurrence of delayed toxic effects in mammals following administration of indirectly acting harmful xenobiotics. In any test system the capacity to bioactivate the compound under test is a necessary prerequisite, and in most short-term test assays this is provided for by adding a metabolic activation system generally consisting of the 9,000 g supernatant fraction of a rat liver homogenate supplied with cofactors. The fruitfly Drosophila melanogaster constitutes an organism well-suited for mutagenicity testing, and it was shown that a number of precarcinogens evoke mutagenic effects in this species. Thus Drosophila is apparently able to metabolize xenobiotics to reactive intermediates, which in turn induce mutagenicity. However, knowledge about the presence and characteristics of the xenobiotic-metabolizing enzymes involved is lacking. Since knowledge of these enzymes contributes to the evaluation and interpretation of observed mutagenic events, this paper described studies concerning some important xenobiotic-metabolizing enzymes of Drosophila. Files were homogenized and subcellular fractions were investigated with respect to enzymatic activities. It was possible to demonstrate cytochrome P-450 and some related mixed-function oxidase activities. Cytochrome b5, epoxide hydrolase, and glutathione S-transferase are also present, while preliminary experiments suggest the presence of UDP-glucosyltransferase and phosphotransferase activities. The enzymes which have been found are discussed with respect to their similarities with rat liver enzymes and their relevance for mutagenicity testing with Drosophila melanogaster.