Human cytochrome P450 reductase can act as a source of endogenous oxidative DNA damage and genetic instability.

Studies with repair-deficient mice and other experiments suggest that oxidative DNA modifications are generated in all types of cells even under physiological conditions and that this type of endogenous DNA damage contributes to spontaneous cancer incidence. However, the cellular sources of reactive oxygen species that are relevant for nuclear oxidative DNA damage are largely unknown. Here, we report that expression of human NADPH-cytochrome P450 reductase (hOR) in cultured V79 Chinese hamster cells gives rise to elevated basal levels of oxidative purine modifications after depletion of glutathione. Also, the basal levels of micronuclei are increased in the hOR-expressing cells, and again t…