Effects of nitrous oxide on macromolecular content and DNA synthesis in rat embryos

Exposure of pregnant rats to the anesthetic gas, nitrous oxide (N2O), has been reported to be teratogenic. This gas decreases activity of the enzyme 5-methyltetrahydrofolate homocysteine methyltransferase (methionine synthetase) and alters the level and distribution of folic acid derivatives in embryonic tissue. Because of their role in purine, thymidine and amino acid metabolism, alterations in the levels of various folate forms could affect macromolecular synthesis. The effect of N2O exposure on the number of somites, the content of DNA, RNA and protein as well as the incorporation of thymidine, deoxyuridine or serine into DNA were determined. Pregnant rats were exposed for 24 hr to 50% N2O-50% O2 beginning on day 10 of gestation. Control animals were exposed to 50% N2-50% O2. Embryos were removed and cultured for 4 hr using a rodent whole embryo culture system in medium containing radiolabeled precursors for DNA. Treatment with N2O had no effect on somite number, RNA or protein content. However, there was a significant decrease in DNA content. There was an increase in the incorporation of thymidine into DNA, but the incorporation of deoxyuridine and serine into DNA was decreased. These data demonstrate that treatment of pregnant rats with N2O results in decreased DNA synthesis and content in exposed embryos.