Primary culture of preneoplastic hepatocytes from rats treated with 2-acetylaminofluorene and clofibrate: relationship between resistance to dimethylnitrosamine and responsiveness of peroxisomes.

Hepatocytes of 2-acetylaminofluorene-induced hyperplastic nodules of rats treated with clofibrate were transferred to primary culture after dispersion by a collagenase perfusion technique. After 48-hr treatment with dimethylnitrosamine (DMN), the resistance to the agent of the cells forming rod-shaped peroxisomes was examined. Catalase activity of the DMN-resistant cells was also determined. At concentrations of 10(-3)M and 10(-4)M DMN, the resistant cell population of hepatocytes with rod-shaped peroxisomes was larger than that of the cells without abnormal peroxisomes. On the other hand, the catalase activity of the attached cells that remained after DMN treatment decreased as the concentration of DMN was increased. The cells showing a stronger induction of the enzyme activity were found to be more sensitive to the cytotoxicity of DMN and they became detached from the culture dishes.