Biomedical Engineering Reference
In-Depth Information
In regard to the mechanism by which MeOH enhances embry-
opathic ROS formation, our preliminary results showing a reduc-
tion in MeOH embryopathies in culture by pretreatment with a
NOX inhibitor suggest that MeOH may activate/induce embry-
onic NOXs that form ROS intracellularly. Conversely, PHS-
mediated bioactivation of MeOH to a free radical intermediate
is unlikely to play a role, as preliminary studies using PHS
inhibition did not alter MeOH-initiated embryopathies in culture.
MeOH did not increase the level of oxidatively damaged DNA in
any tissue in any species, despite enhanced baseline DNA oxida-
tion observed in DNA repair-deficient Ogg1 KO mice, and
enhanced DNA oxidation observed with a ROS-initiating positive
control. Similarly, levels of HNE-His protein adducts, reflecting
free radical-mediated production of the potentially carcinogenic
lipid peroxidation product HNE, were not enhanced by MeOH in
primate bone marrow or spleen, or in rabbit bone marrow or mouse
spleen, although modest increases were observed in rabbit spleen
and mouse bone marrow. These results suggest that it is unlikely
that human environmental exposure to MeOH would cause cancer
via a mechanism involving oxidatively damaged DNA.
ACKNOWLEDGMENT
These studies were supported by grants from the Methanol Foundation
(USA) and the Canadian Institutes of Health Research.
REFERENCES
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Abramov, J.P. and Wells, P.G. (2011) Embryonic catalase protects against
endogenous and phenytoin-enhanced DNA oxidation and embryopathies
in acatalasemic and human catalase-expressing mice. FASEB J. 25, 2188-
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