Evaluation of the developmental toxicity of 4-Bromobenzene using frog embryo teratogenesis assay—Xenopus: Possible mechanisms of action

✍ Scribed by Douglas J. Fort; Timothy L. Propst; Enos L. Stover

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 566 KB
• Volume: 16
• Category: Article
• ISSN: 0270-3211
• DOI: 10.1002/(sici)1520-6866(1996)16:6<307::aid-tcm3>3.0.co;2-m

✦ Synopsis

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 CHOand 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 (MF0)-mediated metabolism may play an important role in the developmental toxicity of 4-bromobenzene in vitro. Furthermore, both epoxide hydrolase and glutathione conjugation appeared to be responsible for activated 4-bromobenzene detoxification. o 1997 Wiley-Liss, Inc.