The effect of 3′-methyl-4-dimethylaminoazobenzene on foetal rat hepatocytes in culture

In hepatocyte cultures derived from 15-day and 19-day rat foetuses tyrosine aminotransferase accumulates during culture. In 15-day foetal hepatocytes enzyme is not detectable on day 1, whereas enzyme is already present in 19-day foetal hepatocytes at the same time. The effect of the hepatocarcinogen, 3′-methyl-4-dimethylaminoazobenzene (MDAB) on these two populations of differentiating hepatocytes is the subject of this study. This was undertaken to test the proposal that carcinogens may exert their effect on differentiating precursor cells. In cultures of 19-day foetal hepatocytes, accumulation of tyrosine aminotransferase is suppressed by MDAB whereas other liver enzyme markers examined, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, are not depressed. It is inferred from this result that hepatocytes that are about to initiate synthesis of tyrosine aminotransferase are prevented from doing so by the action of the carcinogen. In contrast, the synthesis of phosphoenolpyruvate carboxykinase by these cells which was initiated much earlier in development is unaffected. These findings would be consistent with the concept that carcinogens affect differentiating cells. In 15-day foetal hepatocytes, contrary to expectation, no effect of the hepatocarcinogen could be demonstrated. It is suggested that this may be due to the inability of the very immature hepatocytes to activate the hepatocarcinogen. In agreement with the biochemical data, the 19-day foetal hepatocytes but not the 15-day foetal hepatocytes display altered morphology when exposed to MDAB.