The long-term health effects of chronic exposure to anesthetic gases have been of major concern for the past several years. Of some concern is the possibility that occupational exposure to the anesthetic gas, nitrous oxide (N2O), may increase the incidence of congenital abnormalities and spontaneous abortions in operating room personnel as well as dentists and their assistants. In addition to the occupational risk, dental patients may also be at some increased risk for the production of abnormal offspring. The objective of this research is to determine the mechanism of teratogenicity of N2O. The proposed experiments will test the hypothesis that N2O is teratogenic via its effects on embryonic folic acid levels and metabolism. The rat will be used as an animal model system. In embryonic tissue, N2O inhibits methionine synthetase (MS) activity, one of the key regulatory enzymes in one carbon transfer reactions involving folates. This inhibition leads to alterations in the level of total folates as well as the distribution of various folate forms. The ramifications of changes in folates on embryonic macromolecular synthesis will be examined. In addition, in adult tissues MS activity requires several days to return to control levels. The length of time necessary for recovery of the embryonic enzyme as well as the consequences of enzyme recovery on folate levels and distribution will also be determined. Finally, if it is determined that a folate deficiency is responsible for the teratogenicity of the drug, folic acid supplements will be administered in an attempt to reverse the embryopathic effects of N2O.
