PMID- 21295602
OWN - NLM
STAT- MEDLINE
DCOM- 20110516
LR  - 20131121
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 252
IP  - 1
DP  - 2011 Apr 1
TI  - Altered methanol embryopathies in embryo culture with mutant catalase-deficient 
      mice and transgenic mice expressing human catalase.
PG  - 55-61
LID - 10.1016/j.taap.2011.01.019 [doi]
AB  - The mechanisms underlying the teratogenicity of methanol (MeOH) in rodents, 
      unlike its acute toxicity in humans, are unclear, but may involve reactive oxygen 
      species (ROS). Embryonic catalase, although expressed at about 5% of maternal 
      activity, may protect the embryo by detoxifying ROS. This hypothesis was 
      investigated in whole embryo culture to remove confounding maternal factors, 
      including metabolism of MeOH by maternal catalase. C57BL/6 (C57) mouse embryos 
      expressing human catalase (hCat) or their wild-type (C57 WT) controls, and 
      C3Ga.Cg-Catb/J acatalasemic (aCat) mouse embryos or their wild-type C3HeB/FeJ 
      (C3H WT) controls, were explanted on gestational day (GD) 9 (plug=GD 1), exposed 
      for 24 h to 4 mg/ml MeOH or vehicle, and evaluated for functional and 
      morphological changes. hCat and C57 WT vehicle-exposed embryos developed 
      normally. MeOH was embryopathic in C57 WT embryos, evidenced by decreases in 
      anterior neuropore closure, somites developed and turning, whereas hCat embryos 
      were protected. Vehicle-exposed aCat mouse embryos had lower yolk sac diameters 
      compared to C3H WT controls, suggesting that endogenous ROS are embryopathic. 
      MeOH was more embryopathic in aCat embryos than WT controls, with reduced 
      anterior neuropore closure and head length only in catalase-deficient embryos. 
      These data suggest that ROS may be involved in the embryopathic mechanism of 
      methanol, and that embryonic catalase activity may be a determinant of 
      teratological risk.
CI  - Copyright (c) 2011 Elsevier Inc. All rights reserved.
FAU - Miller, Lutfiya
AU  - Miller L
AD  - Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, 
      Canada.
FAU - Wells, Peter G
AU  - Wells PG
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110203
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - EC 1.11.1.6 (Catalase)
RN  - Y4S76JWI15 (Methanol)
SB  - IM
MH  - Acatalasia/enzymology/genetics
MH  - Animals
MH  - Catalase/*biosynthesis/genetics
MH  - Embryo, Mammalian
MH  - Female
MH  - Fetal Diseases/chemically induced/*enzymology
MH  - Gene Expression Regulation, Enzymologic/*drug effects
MH  - Humans
MH  - Methanol/*toxicity
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Mutation/*genetics
MH  - Pregnancy
EDAT- 2011/02/08 06:00
MHDA- 2011/05/17 06:00
CRDT- 2011/02/08 06:00
PHST- 2010/10/05 00:00 [received]
PHST- 2011/01/25 00:00 [revised]
PHST- 2011/01/27 00:00 [accepted]
PHST- 2011/02/08 06:00 [entrez]
PHST- 2011/02/08 06:00 [pubmed]
PHST- 2011/05/17 06:00 [medline]
AID - S0041-008X(11)00038-X [pii]
AID - 10.1016/j.taap.2011.01.019 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2011 Apr 1;252(1):55-61. doi: 10.1016/j.taap.2011.01.019. 
      Epub 2011 Feb 3.