Protection by coffee against somatic genotoxicity in Drosophila: role of bioactivation capacity.
The protective effects of coffee against somatic mutation and mitotic recombination induced by cyclophosphamide (CPH), mitomycin C (MMC) and urethane (URE) were evaluated in the standard (ST) and high bioactivation (HB) crosses of the wing spot test in Drosophila melanogaster. These two crosses are characterized by different constitutive levels of cytochrome )-450-dependent enzyme activities. 3-day old larvae transheterozygous for the wing cell markers mwh (multiple wing hairs) and flr3 (flare3) were fed until pupation on medium containing a genotoxin alone or its combination with different concentrations of instant coffee. subsequently, the wings of the resulting adult flies were analysed for detecting single spots (mwh or flr3) originating from mutational or recombinational events as well as twin spots (mwh and flr3) originating exclusively from recombination. The results showed high sensitivity of the HB cross to URE. Co-administration of instant coffee was effective in exerting significant dose-related inhibitory effects on the genotoxicity of URE in the ST and the genetically susceptible HB cross. Similarly, coffee showed significant dose-related inhibitory effects on the genotoxicity of MMC in both crosses. The same protective effect was also observed with one concentration of coffee in combination with CPH. Pretreatment of 2-day-old HB larvae with coffee for 24 hr followed by treatment with URE was also effective in significantly reducing the induction of mutation and recombination. The magnitude of the protective effects of coffee against these three genotoxins was independent of the genotype of the larvae used for treatment, that is it was independent of the bioactivation capacity of these larvae. The study demonstrates the suitability of this assay for obtaining qualitative and quantitative data on the result of interactions among a genotoxin, an inhibitor of genotoxicity and bioactivation capacity of the host.
Abraham
S K
SK
Institute of Toxicology, Swiss Federal Institute of Technology (ETH), Schwerzenbach, Switzerland.
Graf
U
U
D000818:Animals; D003069:Coffee / Q000378:metabolism; D003520:Cyclophosphamide / Q000633:toxicity; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004331:Drosophila melanogaster; D005260:Female; D018565:Food-Drug Interactions; D008297:Male; D016685:Mitomycin / Q000633:toxicity; D008938:Mitosis / Q000187:drug effects; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation / Q000187:drug effects; D011995:Recombination, Genetic / Q000187:drug effects; D014520:Urethane / Q000633:toxicity
D003069:Coffee; D009153:Mutagens; D014520:Urethane; D016685:Mitomycin; D003520:Cyclophosphamide; D003577:Cytochrome P-450 Enzyme System