Impaired antioxidant enzyme activity and increased DNA repair enzyme expression in hamster liver tissues related to cholangiocarcinoma development

Abstract

A possible mechanism of liver fluke (Opisthorchis viverrini; Ov) -associated cholangiocarcinoma (CCA) genesis may be imbalance in responses of antioxidant enzymes and/or DNA repair enzymes which are the consequence of oxidative/nitrative stress, arising from inflammatory processes. This study aimed to investigate changes in the expression patterns of antioxidant enzymes, including superoxide dismutase 2 (SOD2) and catalase (CAT), as well as their activities in Ov-associated hamster CCA tissues. Expression of DNA repair enzymes including apurinic endonuclease (APE) and DNA polymerase beta (DNA pol β) was also investigated. Our results showed that SOD2 and CAT levels were increased in CCA-induced liver hamster tissues at every time point during cholangiocarcinogenesis. However, once tumors were well established, activities of both enzymes were significantly decreased. Expression of APE and DNA pol β was increased in the acute phase of Ov infection and this persisted until tumors developed. These findings suggest that a reduction in antioxidant enzymes and an increase in DNA repair enzymes may contribute to DNA translesion-mediated CCA in liver fluke-associated cholangiocarcinogenesis in the hamster model.