Evaluation of the Developmental Toxicity of Benzo[α]Pyrene and 2-Acetylaminofluorene UsingXenopus: Modes of Biotransformation

Publisher Website
Google Scholar
Abstract
The developmental toxicities of benzo[a]pyrene (BAP) and 2-acetylaminofluorene (AAF) were evaluated using FETAX (Frog Embryo Teratogenesis Assay - Xenopus). Young X. laevis embryos were exposed to these two compounds in each of two separate concentration-response experiments with and without an exogenous metabolic activation system (MAS) and/or inhibited MAS. The MAS was treated with cimetidine (CIM), ellipticine (ELL), or α-napthoflavone (α-N) to selectively modulate cytochrome P-450 activity. Bioactivation of both of these compounds was indicated by increased developmental toxicity observed in MAS tests. Results obtained in treated MAS tests indicated that BAP was predominantly activated by Cytochrome P-450 isozyme CYP1 Al. AAF bioactivation was shown to be only partly mediated by CYP1A1/2. Detoxification pathways for these two compounds were investigated by treatment of the MAS with cyclohexene oxide (CHO) and diethyl maleate (DM) to inhibit the epoxide hydroxylase and glutathione conjugation pathways, respectively. Results indicated that epoxide hydroxylase was primarily responsible for the detoxification of BAP, with glutathione conjugation playing a secondary role. Detoxification of AAF by these two pathways was not indicated.

This publication has 15 references indexed in Scilit: