Neoplastic Transformation of Human Epithelial Cells by Ionizing Radiation

Abstract

Ionizing radiation can induce cancers in humans and animals and can cause in vitro neoplastic transformation of various rodent cell systems. There has been, however, very litter studies on radiogenic transformation of human epithelial cells, especially with high-LET radiation. Using energetic heavy ions, we have been able to transform human epidermal keratinocytes and mammary epithelial cells to various stages of transformation. Both cell lines are immortal, anchorage dependent for growth, and non-tumorigenic in athymic nude mice. Experimental results indicated that radiogenic transformation of these cells is a multistep process and that a single exposure of ionizing radiation can cause only one step of transformation. Multihits may be required for transforming human epithelial cells to fully tumorigenic. Simple chromosome analysis with cells cloned at various stages of transformation showed no consistant large termianl deletion in the transformed cells. Some changes of total number of chromosomes, however, were found in the radiation-transformed epidermal keratinocytes.