title: Methanol teratogenicity in mutant mice with deficient catalase activity and transgenic mice expressing human catalase.
abstract: The role of catalase in methanol (MeOH) teratogenesis is unclear. In rodents it both detoxifies reactive oxygen species (ROS) and metabolizes MeOH and its formic acid (FA) metabolite. We treated pregnant mice expressing either high (hCat) or low catalase activity (aCat), or their wild-type (WT) controls, with either MeOH (4g/kg ip) or saline. hCat mice and WTs were similarly susceptible to MeOH-initiated ophthalmic abnormalities and cleft palates. aCat and WT mice appeared resistant, precluding assessment of the developmental impact of catalase deficiency. Catalase activity was respectively increased at least 1.5-fold, and decreased by at least 35%, in hCat and aCat embryos and maternal livers. MeOH and FA pharmacokinetic profiles were similar among hCat, aCat and WT strains. Although the hCat results imply no ROS involvement, embryo culture studies suggest this may be confounded by maternal factors and/or a requirement for higher catalase activity in the hCat mice.
authors.affiliation: Division of Biomolecular Sciences, Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Michelle T
authors.initials: MT
authors.lastname: Siu
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Wiley
authors.forename: Peter G
authors.initials: PG
authors.lastname: Wells
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000196:embryology / Q000201:enzymology / Q000378:metabolism; D000015:Abnormalities, Multiple / Q000139:chemically induced* / Q000196:embryology / Q000201:enzymology / Q000378:metabolism; D020642:Acatalasia / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D002374:Catalase / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D000432:Methanol / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D011247:Pregnancy; D012997:Solvents / Q000032:analysis / Q000493:pharmacokinetics / Q000633:toxicity*; D013723:Teratogens / Q000032:analysis / Q000493:pharmacokinetics / Q000633:toxicity*
chemical_list: D012997:Solvents; D013723:Teratogens; C577219:CAT protein, human; D002374:Catalase; D000432:Methanol