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.