Cytotoxicity of antineoplastic agents on rabbit corneal epithelium in vitro

Abstract

AbstractWe studied the cytotoxic effects of antineoplastic agents in vitro including cytosine arabinoside (Ara-C), methotrexate, melphalan, 5-fluorouracil (5-FU), and triethylenethiophosphoramide (thiotepa), using rabbit corneal epithelial cell primary tissue cultures. Twenty-four hour [3H]thymidine incorporation was measured 6 hr after the addition of drug or vehicle. A dose-response effect was noted for all agents. Significant (p <0.05) inhibition of thymidine incorporation was reached with Ara-C (10−7M), methotrexate (10−3M), melphalan (10-6M), 5-FU (10−4M), and thiotepa (10−4M). Visual inspection of the cultures was a less sensitive indicator of drug-induced cytotoxicity; except for melphalan, drug concentrations much greater than those that inhibited thymidine incorporation did not alter cell morphology. At a concentration of 10−4M, 2′-deoxycytidine, a competitive inhibitor of Ara-C, protected corneal epithelial cells exposed to Ara-C concentrations up to 10−5M. When used alone, concentrations of deo...