Chlorpromazine Phototoxicity: Growth Inhibition and DNA-Interaction in Normal Human Fibroblasts

Abstract

Growth was impaired in normal human skin fibroblasts following treatment with chlorpromazine and long-wave ultraviolet light (UV-A). The degree of impairment was dose dependent to chlorpromazine within the concentration range tested, 2.5-20 microgram/ml, in the presence of UV-A, 1 J/cm2. Pre-irradiated chlorpromazine at a concentration of 20 microgram/ml had no effect on fibroblast growth. Chlorprotixene, a thioxanthene compound structurally similar to chlorpromazine at a concentration of 10 microgram/ml, was not phototoxic in this system. The effects of chlorpromazine and UV-A on fibroblast DNA were studied using the technique of zone sedimentation in alkaline sucrose. In the absence of light chlorpromazine did not affect sedimentation of DNA. After UV-A irradiation at 20 degrees or 0 degrees C in the presence of chlorpromazine, labeled DNA sedimented more slowly indicating that it had been reduced to smaller fragments. No evidence for interstrand DNA cross-links was found. Chlorpromazine alone or in combination with UV-A did not alter the size of the DNA. These results with cultured fibroblasts indicate that the phototoxic action of chlorpromazine at 366 nm is at least partially explained by interaction with DNA and is not due to the effects of cytotoxic photoproducts.