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) genesismay be imbalance in responses of antioxidant enzymes and/or DNA repair enzymes which are the consequenceof oxidative/nitrative stress, arising from inflammatory processes. This study aimed to investigate changes inthe 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 includingapurinic endonuclease (APE) and DNA polymerase beta (DNA pol β) was also investigated. Our resultsshowed that SOD2 and CAT levels were increased in CCA-induced liver hamster tissues at every time pointduring cholangiocarcinogenesis. However, once tumors were well established, activities of both enzymes weresignificantly decreased. Expression of APE and DNA pol β was increased in the acute phase of Ov infection andthis persisted until tumors developed. These findings suggest that a reduction in antioxidant enzymes and anincrease in DNA repair enzymes may contribute to DNA translesion-mediated CCA in liver fluke-associatedcholangiocarcinogenesis in the hamster model.