Cell types involved in the expression of foetal aldolases during rat azo-dye hepatocarcinogenesis.

Cellular and subcellular immunolocalization of aldose isozymes and alpha-foetoprotein (AFP) was performed in rat liver during the different stages of carcinogenesis induced by 3'-methyl-4-dimethylaminoazobenzene. During the early stages, double-labelling experiments showed that oval and transitional cells that expressed foetal aldolases did not contain adult aldolase B; this isozyme was only found in small and "normal' hepatocytes. AFP was present in transitional cells and in small hepatocytes. During hyperplastic nodule development, neither foetal aldolases nor AFP were located in hepatocytes. These foetal proteins were still observed in transitional cells. In hepatocellular carcinomas, both foetal proteins (aldolase isozymes and AFP) and adult aldolase B were present in malignant cells. Moreover, during the different stages foetal aldolases were also found in sinusoidal cells. These results indicate that, during azo-dye hepatocarcinogenesis, (a) several cell types synthesize foetal aldolases: oval and transitional cells, hepatoma cells and sinusoidal cells; (b) only hepatoma cells and not hepatocytes located in hyperplastic nodules can express both foetal and adult aldolases. This suggests that in primary, as in transplanted, hepatoma the resurgence of foetal isozymes is the consequence of a disturbance of control gene expression.