Biomedical Engineering Reference
In-Depth Information
decrease in the incidence and completeness of palatal fusion. A specific
effect on cell proliferation was evidenced by reductions in total DNA
content at concentrations of methanol that did not reduce protein
content, and by decreased incorporation of
3
H-thymidine in palatal
mesenchyme. Ethanol appeared to be a more potent inhibitor of palato-
genesis in vitro than methanol. This system probably does not, however,
model the mechanisms inducing cleft palate in vivo, since the critical
period of susceptibility in vivo is during an earlier developmental stage.
In a study designed to elucidate quantitative and qualitative strain
differences in response to methanol, GD 8 C57BL/6J and CD-1 mouse
embryos with 5-7 somites were cultured in the presence of increasing
concentrations of methanol (Degitz et al., 2004b). Embryos were
cultured in 0, 1, 2, 3, 4, or 6mgmethanol/ml for 24 hours and evaluated
for morphological development. Cell death was increased in both
strains in a developmental stage- and region-specific manner at 4
and 6mg/ml after 8 hours of exposure. The proportions of cranial
region cells in S-phase were significantly decreased following 8- and
18-hour exposures to 6mgmethanol/ml culture medium. After 24 hours
of exposure, C57BL/6J embryos had significantly decreased total
protein at 4 and 6mg/ml. Significant developmental effects were
seen at 3, 4, and 6mg/kg, with eye dysmorphology being the most
sensitive endpoint. CD-1 embryos had significantly decreased total
protein at 3, 4, and 6mg/kg, but developmental effects were seen only at
6mg/kg. It was concluded that the C57BL/6J embryos were more
severely affected by methanol in culture than were CD-1 embryos.
5.3.6 Folate Deficiency—A Susceptibility Factor for Methanol
Developmental Toxicity?
Humans and other primates are susceptible to the effects of methanol
exposure associated with formate accumulation because they have
lower levels of hepatic tetrahydrofolate-dependent enzymes involved
in formate oxidation. Pregnant women are often of marginal or deficient
folate status. Tetrahydrofolate-dependent enzymes and critical path-
ways that depend on folate, such as purine and pyrimidine synthesis,
may also play a role in the developmental toxicity of methanol. Studies
