P. Lennartsson et al., p53 expression and TGF-alpha-induced replication of hepatocytes isolated from rats exposed to the carcinogen diethylnitrosamine, CELL BIOL T, 15(1), 1999, pp. 31-39
Previous reports indicate that the expression of transforming growth factor
a (TGF-alpha) is increased in enzyme-altered foci (EAF) arising in livers
of rats treated with a carcinogen. Here we have investigated the effects of
TGF-alpha on EAF cells in vitro. Hepatocytes were isolated from rats that
had received repeated treatment with diethylnitrosamine (DEN) and whose liv
ers contained glutathione S-transferase P (GST-P)-positive EAE Primary cult
ures of GST-P-positive and GST-P-negative hepatocytes were exposed to TGF-a
lpha. TGF-alpha (20-40 ng/ml) increased DNA replication in the GST-P-negati
ve, but not in the GST-P-positive cells. Furthermore, it was shown that thi
s effect on GST-P-negative cells could be blocked by p53 antisense oligonuc
leotides. We conclude that EAF hepatocytes do not respond to TGF-alpha in v
itro. This lack of response may reflect the attenuated expression of p53 in
these cells. These data corroborate previous findings that, in response to
DNA damage, many EAF hepatocytes do not accumulate p53.