Extended abstract:Unlimited life span of human diploid normal epithelial cells (original) (raw)

1995, Radiation Oncology Investigations

Biomedical research into concepts of senescence, apoptosis, and carcinogenesis is almost entirely based on the paradigm that human diploid normal cells are programmed to die after undergoing a certain predetermined number of cell divisions. The paradigm of limited life span is based on observations made almost 30 years ago that normal human cells are difficult to cultivate for extended periods, whereas tumor cells that invariably exhibit numerical and/or structural chromosomal alterations continue to divided in vitro for an infinite period. It should be noted, however, that tumor cells from various human tumors have also been difficult to cultivate for extended periods. Recently, as a result of greater understanding of the nutritional requirements of cultured cells and the identification of growth inhibitory factors, many refinements in tissue culture technology have occurred that have allowed the serial passage of normal cells from a variety of human tissues. Our hypothesis is that, under optimal conditions, diploid normal epithelial cells inherently have an unlimited, not a limited, life span in vitro and that the difficulty of culturing the normal cells for extended periods is due to suboptimum culture conditions. Furthermore, normal cells are not programmed to die after undergoing a predetermined number of divisions, an assumption that was based on the paradigm of limited life span of normal human cells. In support of this hypothesis, for the first time, we have established two normal diploid epithelial cell lines, HPAMl and HPAF1, from the human salivary gland of a male and a female patient, respectively. Both cell lines exhibit diploid karyotypes, normal phenotypes, and are not tumorigenic. Furthermore, the cells produce salivary gland-specific proteins, i.e., a-amylase 1, pro-line-rich protein (PRP), and cystatin, and express the respective genes.