Detection of Transforming Genes from Radiation Transformed Human Epidermal Keratinocytes by a Tumorigenicity Assay

Abstract

Carcinogenic action of ionizing radiation in humans has been well recognized from epidemiological data. There have been, however, very few studies on radiation-induced neoplastic transformation of human cells, particularly, those of epithelial origin, in culture. Recently, we have developed an in vitro human keratinocyte multistep model suitable for the study of human epithelial cell carcinogenesis (1). This was developed following an infection of primary human epidermal keratinocytes with Ad12-SV40 virus leading to the acquisition of an indefinite lifespan in culture, but not the development of malignant phenotype. These immortalized human keratinocytes (RHEK-1) when treated subsequently with either Kirsten murine sarcoma virus (Ki-MSV) (1) or chemical carcinogens, (2) led to the induction of morphological alterations and the development of a malignancy. The availability of this human keratinocyte system led us to determine the potential of X-rays as a carcinogenic agent in human epithelial cells and to characterize the molecular events involved in the development of a radiation-induced malignancy.