Mutagenicity of mixtures of polycyclic aromatic hydrocarbons

Mutagenicity of mixtures of polycyclic aromatic hydrocarbons

263 Studies on metabolism and mutagenicity of nitrosamines and aflatoxin B~ in Drosophila melanogaster In order to compare the activation potency of...

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263

Studies on metabolism and mutagenicity of nitrosamines and aflatoxin B~ in Drosophila

melanogaster In order to compare the activation potency of the xenobiotic-metabolizing enzymes in Drosophila, we carried out experiments with 14C-labelled diethyl- and dimethylnitrosamines (DEN and DMN), and with 7 different Drosophila strains. The aim of these studies was first to analyse the activation potency of different strains and second, to find a correlation between the metabolism of DEN and its potency to induce mutations. Our results indicate that strain differences exist. We found a good correlation between the DEN metabolism rate, and the mutation frequency induced by DEN. Strains with high activation potency turned out to be more sensitive to mutation induction than strains with low activation potency. These findings are in good agreement with in vitro studies carried out with various tissue slices in mammals. In order to study the xenobiotic-metabolizing enzyme-dependent activation of aflatoxin B~ in Drosophila, we treated the strain Hikone-R with 14C-labelled AFB 1 and searched for chloroform-soluble metabolites by the radio-TLC method. According to our findings, aflatoxicol, the reduced form of AFB~, is the major metabolite in Drosophila. We further found aflatoxin Mi, which is metabolized by the MFO and aflatoxin B2a. Other metabolites seem to be formed in Drosophila, but we could not yet identify them.

69 Hubbard, S.A., C.M. Hunt and J.W. Bridges, Robens Institute of Industrial and Environmental Health and Safety, University of Surrey, Guildford, GU2 5XH (Great Britain)

Mutagenicity of mixtures of polycyclic aromatic hydrocarbons Extraction of complex mixtures into fractions for mutagenicity testing does not allow for possible antagonistic and synergistic effects that might occur if a mixture was tested unfractionated. The effect of mixing together certain polycyclic aromatic hydrocarbons has been assessed in the Salmonella/microsome assay. The mutagenicity observed with benzo[a]pyrene with TA98 was significantly increased when the non-mutagenic anthracene (dose range 1-100 /ag/plate) was added to the test. However, the mutagenicity of dimethylbenzanthracene was slightly depressed by anthracene, while the mutagenicity of benzanthracene was unaffected by anthracene. These effects are unlikely to be unique, other mixtures of chemicals may show such effects. However, the results so far indicate the caution that is required when testing complex mixtures. Fractionation of a sample cannot accurately predict the mutagenicity of the sample if it were tested whole.