The MUTYH base excision repair gene protects against inflammation-associated colorectal carcinogenesis.

ABSTRACT: MUTYH DNA glycosylase removes mismatched adenine opposite 7, 8-dihydro-8-oxoguanine (8-oxoG), which is the major mutagenic lesion induced by oxidative stress. Biallelic mutations in MUTYH are associated with MUTYH-Associated polyposis (MAP) and increased risk in colorectal cancer (CRC). We investigated cancer susceptibility associated with MUTYH inactivation in a mouse model of inflammation-dependent carcinogenesis induced by azoxymethane (AOM) and dextran sulphate (DSS). Mutyh-/- mice were more sensitive than wild-type (WT) animals to AOM/DSS toxicity and accumulated DNA 8-oxoG in their gastrointestinal tract. AOM/DSS-induced colonic adenomas were significantly more numerous in Mutyh-/- than in WT animals, and frequently showed a tubulo-villous feature along with high-grade dysplasia and

SUBMITTER: Grasso F 

PROVIDER: S-EPMC4637313 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature