Role of S-adenosylmethionine in DNA synthesis and haemopoiesis

In man, exposure to nitrous oxide (N2O) can produce neurological damage and megaloblastic change in the bone marrow due to inactivation of vitamin B12. Methionine metabolism is interrelated with that of vitamin B12 and folate; the effect of methionine on the impaired DNA synthesis produced by N2O was therefore studied in 17 patients undergoing surgery. 14 were anaesthetised with 50% N2O in oxygen for 3-24 h. The remaining 3 had been exposed to N2O for less than 3 h. All patients developed megaloblastic bone marrow change except 2 of the latter patients whose bone marrows remained normoblastic. The bone marrow was studied biochemically using the deoxyuridine (dU) suppression test. The in vitro addition of small doses of methionine was as effective as vitamin B12 itself in correcting the defective DNA synthesis produced by N2O. It is suggested that N2O impairs methionine biosynthesis, methionine, in the form of S-adenosylmethionine (SAM), being required for DNA synthesis and the prevention of the development of megaloblastic anaemia in man.