EFFECTS OF ETHINYL ESTRADIOL AND EPIDERMAL GROWTH-FACTOR ON DNA-SYNTHESIS IN HUMAN CULTURED-HEPATOCYTES

It has been demonstrated that the liver tumor promoter ethinyl estradiol (EE) potentiates the DNA synthetic response of cultured rat hepatocytes to epidermal growth factor (EGF), probably acting as a comitogen with a growth factor of the EGF/TGF family. The present study investigated the effects of EE and EGF on DNA synthesis in cultures of rat and human hepatocytes obtained from 5 female donors. The cultures were given the following treatments: a. 15 muM EE for 30 h; b. 25 ng/ml of EGF for 12 h; c. combination of treatments a and b. The results obtained in rat hepatocytes confirm that EE potentiates the.DNA synthetic response to EGF, as evaluated by the labelling index. As to human hepatocytes, in only one case the response to EGF produced a significant increase of DNA synthesis and the EE pretreatment did not potentiate this effect. The results of this study indicate that, in contrast to the response observed in rat hepatocytes, EE does not seem to affect the DNA synthesis in primary cultures of human hepatocytes, and the association EE+EGF does not produce any synergic effect.