Reduction of glutathione levels in livers of mice treated with N,N'-bis (2-chloroethyl)-N-nitrosourea.

N-methyl-N-nitrosourea (MNU), N-(2-chloroethyl)-N'-(trans-4-methylcyclohexyl)-N-nitrosourea (methylCCNU), and N,N'-bis(2-chloroethyl)-N-nitrosourea (BCNU) were examined for their effect on glutathione (GSH) levels of various tissues of normal and L1210-leukemic mice. BCNU produced significant decreases in the GSH levels of livers of both groups, but caused no change in the GSH content of the L1210 tumor or in the lungs. The GSH content of the kidneys of L1210 tumor-bearing mice, however, was significantly decreased by BCNU at early time points. A small increase in the liver content of oxidized glutathione could not account for the decrease content of GSH. Methyl CCNU and MNU were without effect on any of the tissues examined. These data are consistent with our previous observation that BCNU is a substrate for GSH S-transferase, and suggest that a GSH-dependent process is an important pathway for the metabolism of BCNU.