Effect of nitrous oxide on haematopoiesis in vitro: biochemical and functional features.

Prolonged exposure to nitrous oxide (N2O) can induce dyshaematopoiesis by causing a functional cobalamin-deficiency state through oxidation of methyl-cobalamin (vitamin B12). Herein, we demonstrate that N2O exposure of murine bone marrow cells in vitro results in both functional and biochemical perturbations. In haematopoietic and bone marrow stromal cells, N2O exposure results in a decrease in methionine synthetase activity with a corresponding increase in homocysteine efflux. In semisolid cultures, N2O inhibits colony formation by cells belonging to the colony forming unit in culture (CFU-C) compartment. In contrast, N2O-exposed stromal cell layers maintain the ability to bind and support the differentiation of haematopoietic progenitor cells upon reseeding. Together, these data suggest that the dyshaematopoiesis seen after exposure to N2O is mediated through a direct inhibitory effect on haematopoietic cells.