PMID- 11931840
OWN - NLM
STAT- MEDLINE
DCOM- 20020610
LR  - 20190623
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 63
IP  - 6
DP  - 2002 Mar 15
TI  - Relative importance of maternal and embryonic microsomal epoxide hydrolase in 
      7,12-dimethylbenz[a]anthracene-induced developmental toxicity.
PG  - 1077-84
AB  - 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 was 
      detected in the serum of wild-type pregnant mice treated with DMBA, but not in 
      that of mEH-null mice. These results suggest that maternal mEH plays a major role 
      in DMBA-induced developmental toxicity, and embryonic mEH is less involved in the 
      toxicity.
FAU - Miyata, Masaaki
AU  - Miyata M
AD  - Division of Drug Metabolism and Molecular Toxicology, Graduate School of 
      Pharmaceutical Sciences, Tohoku University, Sendai, Japan. 
      miyata@mail.pharm.tohoku.ac.jp
FAU - Motoki, Kazuko
AU  - Motoki K
FAU - Tamura, Etsuko
AU  - Tamura E
FAU - Furukawa, Masayuki
AU  - Furukawa M
FAU - Gonzalez, Frank J
AU  - Gonzalez FJ
FAU - Yamazoe, Yasushi
AU  - Yamazoe Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Carcinogens)
RN  - 57-97-6 (9,10-Dimethyl-1,2-benzanthracene)
RN  - 72617-60-8 (7,12-dimethylbenz(a)anthracene-3,4-dihydrodiol)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
SB  - IM
MH  - 9,10-Dimethyl-1,2-benzanthracene/*analogs & 
      derivatives/analysis/metabolism/*toxicity
MH  - Analysis of Variance
MH  - Animals
MH  - Carcinogens/metabolism/*toxicity
MH  - Cell Survival/drug effects
MH  - Embryo, Mammalian/cytology/*drug effects/enzymology
MH  - Epoxide Hydrolases/*metabolism
MH  - Fibroblasts/*drug effects
MH  - Mice
MH  - Mice, Inbred C57BL
EDAT- 2002/04/05 10:00
MHDA- 2002/06/11 10:01
CRDT- 2002/04/05 10:00
PHST- 2002/04/05 10:00 [pubmed]
PHST- 2002/06/11 10:01 [medline]
PHST- 2002/04/05 10:00 [entrez]
AID - S000629520200847X [pii]
AID - 10.1016/s0006-2952(02)00847-x [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2002 Mar 15;63(6):1077-84. doi: 10.1016/s0006-2952(02)00847-x.