Differential effects of dimethyl sulfoxide and sodium butyrate on alpha-fetoprotein, albumin, and transferrin production by rat hepatomas in culture.

Abstract

Radioimmunoassay was used to determine alpha-fetoprotein (AFP), albumin, and transferrin production (ng/10(5) cells/24 h) by two cell lines (7777 and 8994) derived from chemically induced rat hepatomas. alpha-Fetoprotein production was high (2000 to 4400) in 7777, but was very low (0.2 to 0.4) in 8994. Albumin production varied from 0.4-0.8 (7777) to 14-26 (8994). Both lines produced substantial amounts of transferrin (180 to 240 by 7777 and 29 to 42 by 8994). Addition of dimethyl sulfoxide (DMSO, 1 to 4%) or sodium butyrate (BA, 0.5 to 2.0 mM) to the medium inhibited growth in both lines, but 8994 was more sensitive to these agents than 7777. Dimethyl sulfoxide treatment (2 to 4%) resulted in a dose-related decrease (less than 10% of control at 4% DMSO) in AFP, albumin, and transferrin production by 7777, but in 8994, DMSO (1 to 2%) resulted in an increase (up to sixfold) in albumin and transferrin production, without affecting AFP production. By contrast, BA (2 to 4 mM) stimulated the production of all three proteins in both lines, most notably that of albumin (up to sixfold) by 7777 and that of AFP (up to 20-fold) by 8994. It is concluded that both DMSO and BA can enhance the expression of differentiated functions of the hepatoma cell, and that DMSO at the same time can suppress the expression of an oncofetal function. However, neither DMSO nor BA is selective in its effects on specific genes (i.e., normal, adult vs. oncofetal genes), and it appears that their effects may be the result of a more general phenomenon, the expression of which may be related to the stage of differentiation of the cell.