BRAIN CONTAINS INHIBITING FACTORS SPECIFIC TO THE LARGE T-ANTIGEN GENE

SV40 large T-antigen (LTa) gene-induced immortalized rat dopamine-prod ucing nerve cells (1RB(3)AN(27)), which produce LTa protein and divide in vitro, do not divide and do not produce LTa protein when transplan ted into striatum of adult rats. This suggests the presence of LTa gen e-inhibiting factors in brain. Here we report that rat brain soluble f raction (SF) contains factors which specifically inhibit LTa gene acti vity in vitro. The brain SF inhibited LTa protein levels and the growt h of 1RB(3)AN(27) cells and 2RSG cells (LTa gene-induced immortalized rat parotid acinar cells) in vitro, but it stimulated the growth of sp ontaneously immortalized human parotid acinar cells (2HPC8) and had no effect on the proliferation of murine neuroblastoma cells (NBP2) and rat glioma cells (C-6) in culture. In contrast, the liver SF inhibited the growth of all cell lines tested at varying degrees and thus lacke d specificity with respect to LTa gene activity. The presence of speci fic LTa gene-inhibiting factors in the brain and general tumor growth- inhibiting factors in the liver may provide some of the mechanisms of protection against in vivo carcinogenesis. (C) 1998 Elsevier Science I reland Ltd.