Ocular cicatricial disease. Drug effects in vitro on cell proliferation, contraction, and viability.
Fluoroorotate, tunicamycin, and actinomycin D exhibit optimal effects on cell contractility if cells are exposed to the drug for 72 hr, followed by 24 hr of exposure during the contractility assay. Under these conditions, fluoroorotate and tunicamycin inhibit contractility at concentrations very similar to those required to inhibit proliferation, and at higher concentrations affect cell viability. In contrast, the concentrations at which actinomycin D inhibits cell contractility and viability are very similar, and the concentration at which it inhibits cell proliferation is much lower. These results suggest that fluoroorotate and tunicamycin inhibit cell contractility by inhibiting membrane protein glycosylation. Actinomycin D, which inhibits RNA synthesis, appears to block cell contractility only by blocking cell viability, and its most potent effect inhibits only cell proliferation. Daunomycin exhibits very similar effects on cell contractility if cells are exposed to drug for 48 or 72 hr prior to the assessment of contractility, and its effects are not appreciably increased by the further inclusion of the drug for 24 hr during the contractility assay. Daunomycin also has appreciable effects on contractility if cells are exposed to the drug only for the 24 hr of the contractility assay. Similar to actinomycin D, daunomycin inhibits cell contractility and viability at similar concentrations, and inhibits cell proliferation at much lower concentrations. Moreover, daunomycin can appreciably inhibit cell viability in 24 hr of exposure. Therefore, daunomycin appears only to block cell contractility by blocking cell viability, and its most potent effect inhibits only cell proliferation.
Heath
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TD
School of Pharmacy, University of Wisconsin Madison 53706.
Brown
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CS
Stern
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WH
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002921:Cicatrix / Q000188:drug therapy* / Q000473:pathology; D003609:Dactinomycin / Q000494:pharmacology*; D003630:Daunorubicin / Q000494:pharmacology; D009963:Orotic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D011817:Rabbits; D012164:Retinal Diseases / Q000188:drug therapy* / Q000473:pathology; D012867:Skin; D014415:Tunicamycin / Q000494:pharmacology*
D014415:Tunicamycin; D003609:Dactinomycin; D009963:Orotic Acid; C001242:5-fluoroorotic acid; D003630:Daunorubicin