Concentration and duration dependent induction of hepatocyte DNA synthesis in male B6C3F1 mice exposed to phenobarbital (PB)

A common effect of many hepatocarcinogens in the male B6C3F1 mouse is their induction of hepatocyte DNA synthesis and cell proliferation. The present study was undertaken to examine the time course and dose dependency of this cell proliferation following continuous treatment with the hepatic carcinogen PB. Male B6C3F1 mice received either 0, 20, 100, or 500 mg/l of PB in their drinking water. After 1, 2, 4, 6, and 13 weeks, 3 mice from each treatment group were killed and DNA synthesis was evaluated by autoradiography. Three days prior to sampling each mouse received an osmotic minipump containing 3HTdR. Only the 500 and 100 mg/l PB treatments induced DNA synthesis. DNA synthesis peaked after 2 weeks of PB treatment with a 15 fold increase over control with 500 mg/l and a 10 fold increase with 100 mg/l. At 6 and 13 weeks of treatment, none of the PB doses increased DNA synthesis over control values. Thus, PB induced a time and concentration dependent increase in DNA synthesis that peaked at 2 weeks and returned to control levels by 6 weeks