Early effects of chemical carcinogens as compared to induced cell proliferation. I. Flow microfluorimetry

Acridine orange-stained rat liver cells have been analyzed by flow microfluorimetry either after i.p. injection of 0.6 and 5.4 mg/kg of dimethylnitrosamine or 18 hr after partial hepatectomy. Treatment with dimethylnitrosamine induced a marked increase in the fraction of cells with higher green fluorescence intensity which can be related to a greater number of chromatin primary binding sites, and a decrease in the fraction of cells with higher red fluorescence intensity corresponding to a lower amount of cellular RNA. Contrary to the carcinogen-induced early changes towards a more relaxed uncoiled structure, as well as an apparent uncoupling between chromatin-DNA structural alterations and total RNA synthesis, could be first events in the carcinogenetic process.