Mitosis in hepatocytes is generally associated with elevated levels of the target polypeptide of a liver carcinogen.

Rat hepatocytes have previously been found to contain in their cytoplasm a 14,000-dalton polypeptide that: is markedly and specifically increased in concentration during the infrequent mitoses that occur in hepatocytes of adult normal liver; is apparently related to a 17,500-dalton polypeptide that is tightly bound to the chromatin of nuclei of normal adult liver; is the principal covalent target of the carcinogen, N-2-fluorenylacetamide (FAA; 2-acetylaminofluorene), early during liver carcinogenesis; is present at highly elevated levels in the proliferating hepatocytes of hyperplastic foci brought about by the two liver carcinogens, FAA and 3'-methyl-4-dimethylaminoazobenzene; and is present at a greatly depressed level in the mitotically nonresponsive parenchyma that surrounds these hyperplastic foci. In the present investigation, we examined the levels of the two polypeptides in hepatocytes undergoing cell division at different rates in livers of diverse normal and regenerative states. Using immunohistochemical techniques, both polypeptides were detected in developing hepatocytes in as early as 15- and 19-day rat fetuses. With the increasing maturity of fetal and neonatal livers in normal rats, a greater percentage of dividing hepatocytes exhibited a higher concentration of the 14,000-dalton target polypeptide than that seen in adjacent interphase hepatocytes. The percentage of mitotic hepatocytes with an elevated level of the polypeptide increased progressively with hepatic development as follows: 38% in 15-day fetuses, 50% in 19-day fetuses, 85% in 1-day neonates, between 79% and 93% until 28 days of age, and finally, 99% in normal adults.(ABSTRACT TRUNCATED AT 250 WORDS)