THE RADIOSENSITIVITY OF HUMAN KERATINOCYTES - INFLUENCE OF ACTIVATED C-H-RAS ONCOGENE EXPRESSION AND TUMORIGENICITY

We have investigated the gamma-ray sensitivity of several activated c-H-ras (EJ) containing clones that have been established after transfection of the spontaneously immortalized non-tumorigenic human keratinocyte cell line HaCaT. The clones were grouped according to their tumorigenic potential after subcutaneous injection into nude mice, and fell into three classes: Class I clones A-4 and I-6 are non-tumorigenic and express very low levels of c-H-ras mRNA and no mutated ras protein (p21); Class II clones I-5 and I-7 grow to large (benign) epidermal cysts, express intermediate to high c-H-ras mRNA and variable levels of mutated ras p21 protein with clone I-5 expressing little and clone I-7 expressing high levels of p21; Class III clones II-3 and II-4 grow to solid squamous cell carcinomas, express high c-H-ras mRNA and high level of mutated p21 ras protein similar to clone I-7. Comparison of the single-hit multitarget or linear-quadratic survival curve parameters, and survival at 2 Gy (S2) indicate that there appears to be no general correlation with either activated c-H-ras expression level or tumorigenic potential, and increased radioresistance.