The effect of carcinogens on the accumulation of tyrosine aminotransferase by foetal rat hepatocytes in culture.

The hepatocarcinogen 3'-methyl-4-dimethyl-aminoazobenzene (MDAB) suppresses the accumulation of tyrosine aminotransferase in cultured foetal hepatocytes. Experiments involving liver derived from foetuses of various ages reveals that a response is only obtained with rats older than 16-day gestation. It has been proposed that the lack of an effect in less mature hepatocytes is due to their inability to activate the carcinogen. Chemically synthesized analogues of MDAB which are considered likely to be activated forms of the procarcinogen are shown to be effective in the less mature cells. This supports the proposal that these cells may be unresponsive because they are unable to activate MDAB. Tests with other carcinogens reveal that the hepatocarcinogen dimethylbenzanthracene is also effective in 19-day gestation hepatocytes. However, the non-hepatocarcinogens azaserine and benz(a)pyrene are ineffective. Treatment with MDAB is shown not to alter the level of steroid receptor and reduce its translocation into the nucleus, suggesting that this is not the mechanism by which TAT is suppressed. The effect of the tumour promoter phorbol-myristate acetate (PMA) administered together with MDAB was shown not to modify the response to the carcinogen alone.