Endogenous glutathione levels modulate the frequency of both spontaneous and long wavelength ultraviolet induced mutations in human cells

Abstract

Spontaneous and induced mutations at the hypoxanthine guanine phosphoribosyl transferase locus have been measured in cultured human lymphoblastoid (TK6) cell populations under conditions in which cellular glutathione has been severely depleted by overnight treatment with buthionine-S,R-sulfoximine. At maximum levels of glutathione depletion, the increase in spontaneous frequency is at least 5-fold, a finding consistent with the possibility that cellular redox state can modulate the levels of pre-mutagenic damage arising as a result of normal metabolism in cultured human cells. Glutathione depletion does not lead to a significant enhancement in the frequency of mutants that arise as a result of irradiation at 313 nm but does lead to a 3-fold increase in mutations resulting from irradiation at 365 nm. These results indicate that glutathione may quench reactive intermediates that would otherwise lead to spontaneous mutations as well as a fraction of UVA radiation-induced premutagenic damag