EFFECT OF NITROUS-OXIDE EXPOSURE ON MATERNAL AND EMBRYONIC S-ADENOSYLMETHIONINE LEVELS AND ORNITHINE DECARBOXYLASE ACTIVITY

Nitrous oxide is suspected to be a developmental toxicant in humans. T he anesthetic does produce increases in the resorption and malformatio n frequencies in rodents. The mechanism for the drug's developmental t oxicant effects is unknown. Embryonic DNA synthesis is decreased; howe ver, this decrease does not appear to be due to depressed levels of ad enine or guanine. In this investigation, we examined the effect of N2O on maternal and embryonic S-adenosylmethionine (AdoMet) levels and or nithine decarboxylase (ODC) activity, and the effect of exogenous meth ionine (Met) on these parameters was also examined. AdoMet and ODC are involved in polyamine synthesis, and polyamines are involved in regul ation of macromolecular synthesis. Pregnant rats were treated with N2O for 24 hours beginning on the morning of day 10 of gestation. There w as no effect of N2O on maternal hepatic AdoMet or S-adenosylhomocystei ne (AdoHcy) levels; there was also no effect on embryonic AdoMet. Embr yonic AdoHcy could not be detected in many of the samples; however, N2 O treatment did significantly increase the number of embryonic samples in which AdoHcy was detectable. ODC activity was not affected by eith er treatment in dams but was increased by N2O in embryos. It is possib le that the embryotoxic effect of this anesthetic is mediated by alter ations in the AdoMet to AdoHcy ratio or to changes in ODC activity and polyamine synthesis.