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. The anesthetic does produce increases in the resorption and malformation frequencies in rodents. The mechanism for the drug's developmental toxicant effects is unknown. Embryonic DNA synthesis is decreased; however, this decrease does not appear to be due to depressed levels of adenine or guanine. In this investigation, we examined the effect of N2O on maternal and embryonic S-adenosylmethionine (AdoMet) levels and ornithine decarboxylase (ODC) activity, and the effect of exogenous methionine (Met) on these parameters was also examined. AdoMet and ODC are involved in polyamine synthesis, and polyamines are involved in regulation of macromolecular synthesis. Pregnant rats were treated with N2O for 24 hours beginning on the morning of day 10 of gestation. There was no effect of N2O on maternal hepatic AdoMet or S-adenosylhomocysteine (AdoHcy) levels; there was also no effect on embryonic AdoMet. Embryonic AdoHcy could not be detected in many of the samples; however, N2O treatment did significantly increase the number of embryonic samples in which AdoHcy was detectable. ODC activity was not affected by either treatment in dams but was increased by N2O in embryos. It is possible that the embryotoxic effect of this anesthetic is mediated by alterations in the AdoMet to AdoHcy ratio or to changes in ODC activity and polyamine synthesis.
Hansen
D K
DK
Division of Reproductive and Developmental Toxicology, Food and Drug Administration, Jefferson, Arkansas 72079-9502.
Knowles
B J
BJ
Fullerton
F R
FR
Poirier
L A
LA
D000818:Animals; D004622:Embryo, Mammalian / Q000737:chemistry / Q000187:drug effects*; D005260:Female; D008099:Liver / Q000737:chemistry / Q000187:drug effects*; D008715:Methionine / Q000494:pharmacology; D009609:Nitrous Oxide / Q000633:toxicity*; D009955:Ornithine Decarboxylase / Q000032:analysis / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D012435:S-Adenosylhomocysteine / Q000032:analysis; D012436:S-Adenosylmethionine / Q000032:analysis / Q000187:drug effects*
D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D008715:Methionine; D009955:Ornithine Decarboxylase; D009609:Nitrous Oxide