S-nitrosoglutathione reductase deficiency increases mutagenesis from alkylation in mouse liver.

ABSTRACT: In human hepatocellular carcinoma (HCC) and many other cancers, somatic point mutations are highly prevalent, yet the mechanisms critical in their generation remain poorly understood. S-nitrosoglutathione reductase (GSNOR), a key regulator of protein S-nitrosylation, is frequently deficient in human HCC. Targeted deletion of the GSNOR gene in mice can reduce the activity of the DNA repair protein O (6)-alkylguanine-DNA alkyltransferase (AGT) and promote both carcinogen-induced and spontaneous HCC. In this study, we report that following exposure to the environmental carcinogen diethylnitrosamine, the mutation frequency of a transgenic reporter in the liver of GSNOR-deficient mice (GSNOR(-/-)) is significantly higher than that in wild-type control. In wild-type mice, diethylnitrosamine trea

SUBMITTER: Leung J 

PROVIDER: S-EPMC3643423 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature