Fort D J, Propst T L, Stover E L
Laboratory Services Division, Stover Group, Stillwater, Oklahoma 74076, USA.
Teratog Carcinog Mutagen. 1996;16(6):307-15. doi: 10.1002/(SICI)1520-6866(1996)16:6<307::AID-TCM3>3.0.CO;2-M.
Potential mechanisms of 4-bromobenzene-induced developmental toxicity were evaluated using frog embryo teratogenesis assay-Xenopus (FETAX). Early X, laevis embryos were exposed to 4-bromobenzene in two separate definitive concentration-response tests with and without an exogenous metabolic activation system (MAS) or selectively inhibited MAS. The MAS was treated with carbon monoxide (CO) to modulate P-450 activity, cyclohexene oxide (CHO) to modulate epoxide hydrolase activity, and diethyl maleate (DM) to modulate glutathione conjugation. Addition of the intact MAS, and particularly the CHO- and DM-inhibited MASs, dramatically increased the embryo lethal potential of 4-bromobenzene. Addition of the CO-inhibited MAS decreased the developmental toxicity of activated 4-bromobenzene to levels approximating that of the parent compound. Results from these studies suggested that a highly toxic arene oxide intermediate of 4-bromobenzene formed as the result of mixed function oxidase (MFO)-mediated metabolism may play an important role in the development toxicity of 4-bromobenzene in vitro. Furthermore, both epoxide hydrolase and glutathione conjugation appeared to be responsible for activated 4-bromobenzene detoxification.
