The cell cycle distribution of cultured human retinal pigmented epithelial cells under exposure of anti-proliferative drugs.
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.
Wu
Wen-Chuan
WC
Department of Ophthalmology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. d84011@kmu.edu.tw
Kao
Ying-Hsien
YH
Tseng
Han-Yi
HY
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
D005938:Glucocorticoids; D019384:Nucleic Acid Synthesis Inhibitors; D016685:Mitomycin; D003907:Dexamethasone; D001973:Bromodeoxyuridine; D005472:Fluorouracil; D003630:Daunorubicin