Genetic and biochemical investigation on chloral hydrate in vitro and in vivo.
Chloral hydrate (CH), a metabolite of trichloroethylene (TCE), was studied in vitro using the D7 diploid strain of Saccharomyces cerevisiae, with and without a mammalian microsomal activation system (S9 fraction), and in vivo by intrasanguineous host-mediated assay (HMA). The in vivo effects on the hepatic microsomal monooxygenase induced by CH in mice pretreated with beta-naphthoflavone (beta-NF) and Naphenobarbital (PB) were also investigated. Chloral hydrate induced a significant increase of mitotic gene conversion in D7 strain both in vivo and in vitro. The enzymatic determinations in mice showed a decrease in aminopyrine N-demethylase (APD) and p-nitroanisole O-demethylase (p-NAD) activities (about 37% and 29% respectively) after one acute dose of CH. Moreover, stability experiments, carried out in the conditions of the liver microsomal assay (LMA), showed an increase of residual activity, after 1 h of preincubation with respect to the control (about 22% and 9% for APD and p-NAD respectively).
D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000818:Animals; D001711:Biotransformation; D002697:Chloral Hydrate / Q000633:toxicity*; D005800:Genes, Fungal / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008168:Lung / Q000187:drug effects; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics
D009153:Mutagens; D002697:Chloral Hydrate; D000633:Aminopyrine N-Demethylase