Cell-density-dependent expression of Cyp1a2 gene in monolayer-cultured adult mouse hepatocytes.

Expression of Cyp1a1 and Cyp1a2 genes was investigated in adult C57BL/6NCrj mouse hepatocytes for up to 5 days after transfer to monolayer culture. CYP1A1 mRNA was substantially induced by treatment with 3-methylcholanthrene during the observation period, independently of the seeded cell density. However, expression of CYP1A2 mRNA was dependent on cell density and was higher in cells cultivated at lower density. With increasing culture period the expression was decreased, so that only negligible levels were evident by day 5, and reduced expression of constitutive and induced CYP-1A2 mRNA became apparent earlier in more densely seeded cells. This was not related to differences in numbers of inducer molecules per cell. While mouse hepatocytes incorporated tritium-labeled thymidine under the given culture conditions, induction of expression of the two Cyp1a genes did not show any direct relationship with DNA synthesizing activity. These observations suggest some role for Cyp1a2 during changes in physiological state.