Comitogenic effects of @entity172 on DNA synthesis induced by various growth factors in cultured female XXXX hepatocytes.

@entity172 @entity5 @entity2082 @entity10494 @entity53 @entity665 @entity35
@entity2082 is a weak complete carcinogen and potent @entity5 promoter. In vivo, @entity2082 causes a rapid but transient increase in liver growth, whereas in cultured female hepatocytes it enhances DNA synthesis induced by epidermal growth factor and is thus classified as a comitogen. The objectives of this study were to determine: (a) whether @entity53 also has comitogenic activity; (b) whether the comitogenic effects of @entity172 extend to complete hepatic mitogens other than epidermal growth factor and (c) whether inhibition of hepatocyte DNA synthesis by transforming growth factor-beta can be blocked by @entity53 . Female @entity35 hepatocytes in primary culture were exposed to @entity53 with and without various growth factors, and we determined DNA synthesis by measuring @entity665 incorporation into extracted DNA or by determining the nuclear labeling index by means of autoradiography. The results show that @entity53 , like @entity2082 , has comitogenic activity for epidermal growth factor, although it is somewhat less potent. Four complete hepatic mitogens showed different abilities to stimulate DNA synthesis, with hepatocyte growth factor > transforming growth factor-alpha > epidermal growth factor > @entity10494 . @entity53 enhanced DNA synthesis occurring in response to all four of these complete hepatic mitogens. This finding suggests that the mechanism of @entity172 comitogenesis may involve effects at a point where the different signal-transduction pathways leading from the growth factors converge. The level of @entity172 -mediated enhancement of DNA synthesis was similar for all four mitogens, ranging from 1.5 to 2.2-fold, depending on the experiment. Furthermore, determination of the nuclear labeling index showed that @entity172 enhancement of DNA synthesis was associated with an increase in the percentage of hepatocytes that responded to the growth factors. Finally, @entity53 did not specifically block the growth-inhibitory effects of transforming growth factor-beta.
