title: Apurinic/apyrimidinic endonuclease 1, the sensitive marker for DNA deterioration in dextran sulfate sodium-induced acute colitis.
abstract: Mutations in mismatch repair (MMR) genes are commonly associated with the development of colorectal cancer. Additionally, base excision repair, which involves apurinic/apyrimidinic endonuclease 1 (APE1), recognizes and eliminates oxidative DNA damage. Here, we investigated the possible roles of APE1 in dextran sulfate sodium (DSS)-induced acute colitis using the young rat model. Four-week-old Sprague-Dawley rats were administered 2% DSS in drinking water for 1 week. MMR and APE1 expression levels were assessed by western blotting and immunohistochemistry. Following DSS treatment, growth of young rats failed and the animals had loose stools. Together with the histological changes associated with acute colitis, APE1 and MSH2 levels increased significantly at 3 and 5 days after DSS treatment, respectively. The difference between APE1 and MSH2 expression was significant. DSS-induced DNA damage and subsequent repair activity were evaluated by staining for 8-hydroxy-deoxyguanosine (8-OHdG) and APE1, respectively; 8-OHdG immunoreactivity increased throughout the colonic mucosa, while APE1 levels in the surface epithelium increased at an earlier timepoint. Taken together, our data suggest that changes in APE1 expression after DSS treatment occurred earlier and were more widespread than changes in MMR expression, suggesting that APE1 is more sensitive for prediction of DNA deterioration in DSS-induced colitis.
authors.affiliation: Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: In-Youb
authors.initials: IY
authors.lastname: Chang
authors.forename: Jin Nam
authors.initials: JN
authors.lastname: Kim
authors.forename: Young Hee
authors.initials: YH
authors.lastname: Maeng
authors.forename: Sang Pil
authors.initials: SP
authors.lastname: Yoon
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D016264:Dextran Sulfate / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016264:Dextran Sulfate; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase