ARTICLE NO 0025 Subchronic Effects of Dieldrin and Phenobarbital on Hepatic DNA Synthesis in Mice and Rats

Dieldrin, an organochlorine pesticide, has been shown to be hepatocarcinogenic in mice but not rats. Phenobarbital, in con-trast, induces hepatic tumors in both mice and rats. Previous stud-ies have shown that acute dietary exposure of rats or mice to either dieldrin or phenobarbital produces several liver changes, including centrilobular hypertrophy, induction of hepatic cytochrome P450, and increased liver weight. The present study examined the sub-chronic effect of dieldrin (0.1, 1.0, 3.0, 10.0 mg dieldrin/kg diet) and phenobarbital (10, 50, 100, 500 mg phenobarbital/kg diet) on the induction of hepatic DNA synthesis and hepatocyte lethality in male B6C3F1 mice and male F344 rats. Eight-week-old animals were treated as above and evaluated for hepatic DNA synthesis after 7, 14, 21, 28, and 90 days of continual treatment to dieldrin or phenobarbital. Maximal induction of hepatic DNA synthesis in mice was seen at the 14-, 21-, and 28-day sampling times. In rats