title: The cell cycle distribution of cultured human retinal pigmented epithelial cells under exposure of anti-proliferative drugs.
abstract: It has been well documented that RPE cells play an important role in the formation of proliferative vitreoretinopathy (PVR). We studied the effects of four most widely used anti-proliferative drugs, i.e., 5-fluorouracil (5-FU), daunomycin (DM), mitomycin C (MMC) and dexamethasone (DEX) in an in vitro model system (cultured human RPE). The cells treated with indicated concentrations of drugs for 48 h were harvested for DNA content analysis. In addition, a time course study with constant dosage of drugs was performed. The results revealed that, after incubation for 48 h, an increased percentage (31.1%) of S phase cells was noted with exposure to MMC (10 ng/ml). It was confirmed by 5-bromodeoxyuridine (BrdU) incorporation test that this increase does not result from higher transition rate from G1 to S phase. The cells of G2/M phase markedly increased from 13.8% to 29.7% with 10 ng/ml DM. We also demonstrated that 5-FU and MMC treatment led to cell accumulation at S phase and DM treatment resulted in cell accumulation at G2/M phase, These findings were compatible with their pharmacological mechanisms. Development of an in vitro model using cultured human RPE to study the effects of various anti-proliferative drugs on cell cycle can provide a rapid, safe and inexpensive method for selection of drugs used for management of PVR.
authors.affiliation: Department of Ophthalmology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. d84011@kmu.edu.tw
authors.forename: Wen-Chuan
authors.initials: WC
authors.lastname: Wu
authors.forename: Ying-Hsien
authors.initials: YH
authors.lastname: Kao
authors.forename: Han-Yi
authors.initials: HY
authors.lastname: Tseng
mesh_terms: D001973:Bromodeoxyuridine / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003630:Daunorubicin / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D005472:Fluorouracil / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D016685:Mitomycin / Q000494:pharmacology*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology*; D010857:Pigment Epithelium of Eye / Q000166:cytology* / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; D019384:Nucleic Acid Synthesis Inhibitors; D016685:Mitomycin; D003907:Dexamethasone; D001973:Bromodeoxyuridine; D005472:Fluorouracil; D003630:Daunorubicin