DNA in rat hepatocyte nuclei: effects of treatment with low levels of carbon tetrachloride and (or) chlordane

Abstract

The effects of low-level, chronic feeding of the insecticide chlordane on the cytochemistry of the hepatocyte nuclei of male nits, with or without liver cirrhosis, were determined. Chlordane was given orally at 0.1 mg kg−1 day−1. Cirrhosis was induced by exposure of the animals to carbon tetrachloride (CCl4) vapours twice weekly for 10 weeks. The animals were killed after 20 weeks and the Feulgen-stained hepatocyte nuclei examined microspectrophotometrically for nuclear size, DNA content, and the degree of chromatin condensation. The five experimental groups were: (A) control; (B) chlordane only for 20 weeks; (C) cirrhosis only (CCl4 weeks 0–10); (D) chlordane (weeks 0–20) plus cirrhosis; (E) cirrhosis (CCl4, weeks 0–10) followed by chlordane (weeks 10–20). All treatments significantly (p < 0.01) increased nuclear size. Although DNA contents were not affected by chlordane alone, in cirrhotic animals treatment with chlordane caused significantly higher DNA contents than that in cirrhotics not receiving chlordane. This suggests that hepatic dysfunction increases the liver's sensitivity to respond to chlordane. Chromatin condensation was decreased by chlordane in both healthy and cirrhotic animals; animals with cirrhosis, but not receiving chlordane, had more condensed chromatin than the controls.The results of this study show that computer analysis of images of Feulgen-stained nuclei is a highly sensitive technique to detect the effects of chemicals on the degree of chromatin condensation even at dosage levels below the no-effect levels previously reported.