Cultures of skin fibroblasts from normal and cancer-prone individuals, as well as neoplastic cells transformed in culture or in vivo, are utilized in evaluating the relationship between radiation-induced chromosomal DNA damage, deficient DNA repair, cancer susceptibility and malignant neoplastic transformation. An increased incidence of chromatid damage after x-irradiation during GS phase of the cell cycle is associated with both a predisposition to cancer and malignant transformation and may provide the basis for a test for cancer susceptibility. A genetic basis for this rediosensitivity is indicated from studies with somatic cell hybrids between normal and malignant cells. The chromosomal radiosensitivity appears to result from deficient DNA repair during G2. Another aspect of this project is to develop a reproducible transformation system with human epidermal keratinocytes as an in vitro model for following the progression of biologic and biochemical changes leading to neoplastic transformation. An associated problem is to identify cytomorphologic changes diagnostic of neoplastic transformation to facilitate transfection and transformation studies. Efforts are in progress to develop a biochemical correlate of enhanced G2 chromosomal radiosensitivity to provide a more rapid assay for cancer susceptibility and to understand the DNA repair deficiencies of cancer-prone individuals.
