Relative importance of maternal and embryonic microsomal epoxide hydrolase in 7,12-dimethylbenz[a]anthracene-induced developmental toxicity

Biochemical Pharmacology
M MiyataYasushi Yamazoe

Abstract

Microsomal epoxide hydrolase (mEH) catalyzes the hydrolysis of epoxide intermediates derived from drugs and environmental chemicals. The response of in vivo (embryo) and in vitro (embryo fibroblast) tests were analyzed using mEH-null and wild-type mice to determine the relative role of maternal and embryonic mEH in the developmental toxicity induced by 7,12-dimethylbenz[a]anthracene (DMBA). Embryos derived from DMBA-treated [50mg/kg, daily from gestational day (GD) 11 to GD 15] dams were analyzed. Although weight (P=0.0009) and crown-rump length (P=0.0003) of wild-type fetuses on GD 18 were significantly lower than those of mEH-null fetuses, respectively, no significant difference was found between mEH-null and heterozygous fetuses of mEH-null dams. Cell viability was decreased to 50% in wild-type mouse embryo fibroblasts (MEFs) treated with 3 microM DMBA, but no significant decrease was found in mEH-null MEFs. DMBA-3,4-diol produced a significant decrease in cell viability and suppressed the proliferation of wild-type MEFs at a 10-fold lower concentration than did DMBA. Although mEH protein was expressed in liver microsomes from wild-type embryos (GD 15), DMBA-3,4-diol was not detected among the DMBA metabolites. However, it w...Continue Reading

References

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Citations

Jul 24, 2003·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Masaaki Miyata
Aug 20, 2002·Japanese Journal of Pharmacology·Masaaki MiyataYasushi Yamazoe
Feb 11, 2004·Proceedings of the National Academy of Sciences of the United States of America·Toshiki ItohStuart Linn
Feb 7, 2014·Biology of Reproduction·Jackson NteebaAileen F Keating
Mar 19, 2003·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Masaaki MiyataYasushi Yamazoe

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