Neoplastic transformation of C3H mouse embryo 10T1/2 cells by 8-methoxypsoralen plus UVA radiation

The effect of 8-methoxypsoralen plus UVA radiation (PUVA) on cell killing and induction of transformation was studied in the C3H mouse embryo 10T1/2 cell line. Dose-response data for both survival and transformation were obtained as a function of 8-methoxypsoralen (8-MOP) concentration and UVA dose. PUVA treatment caused cell death and induced transformation in a dose-dependent manner. Treatment of cells with 8-MOP alone (10 micrograms/ml) or UVA alone (90 J/m2) had no effect on either cell killing or transformation. The product of 8-MOP concentration and UVA dose calculated at 10% survival and 10(-3) transformation frequency levels were quite similar regardless of 8-MOP concentration or UVA dose. This suggests that there exists a simple reciprocal relationship between 8-MOP concentration and UVA dose. Both type II and type III foci induced by PUVA treatment were tumorigenic in vivo. These data provide further evidence for the carcinogenicity of PUVA treatment. In addition, the system described here could serve as a valuable model for studying the relationships between transformation and the specific cellular and molecular lesions induced by PUVA treatment.