ATP INHIBITION OF PROLIFERATION OF IMMORTALIZED HUMAN FIBROBLASTS IS GREATER-THAN THAT OF NORMAL HUMAN-DIPLOID FIBROBLASTS

It is known that cancers develop by a multi-step process. Normal cells are first immortalized, and then transformed into tumorigenic cells. Normal human cells are very rarely immortalized, but once they are, th ey are relatively easily transformed into tumorigenic cells. This indi cates that the immortalization step plays a critical part in the devel opment of human cancers. Thus, elucidation of the mechanisms of this s tep would shed light on the process of carcinogenesis in human cells. To understand the causes of immortalization, it is important to determ ine the differences in cellular phenotype between immortalized and nor mal human cells. In this study, we found that immortalized human fibro blasts were more sensitive to the growth inhibitory effects of ATP tha n normal human fibroblasts. ADP was as effective as ATP, but AMP, aden osine, and phosphoric acid were not. These results indicate that a hig h-energy bound of ATP and ADP may contribute to the growth inhibition of the cells. When the immortalized cells were pulse-labeled with [P-3 2]-ATP, 30-, 31-, 33- and 40-kDa membrane fraction proteins were more prominently labeled in the immortalized cells than in the normal cells . At present, the characteristics of these proteins are being investig ated.