FEASIBILITY OF ADMINISTERING 5-BROMO-2'-DEOXYURIDINE (BRDU) IN DRINKING WATER FOR LABELING S-PHASE HEPATOCYTES IN MICE AND RATS

Abstract

The S-phase hepatocyte labeling index (LI) in rodents has been routinely evaluated by using the labeling agent 5-bromo-2' -deoxyuridine (BrdU) administered by surgically implanted osmotic minipumps or intraperitoneal injections. In this study, BrdU was administered to untreated B6C3F1 mice and F344 rats in drinking water (40, 60, and 80 mg/100 mL) or by osmotic minipumps (30 mg/mL) for 24, 48, or 72 h. In addition, one group of rats, of which half were singly housed, and one group of mice were treated with the hepatotoxic agent furan or corn oil vehicle while exposed for 7 days to BrdU in drinking water (80 mg/100 mL) or by osmotic minipumps. There was an additive increase in the LI of the minipump-dosed mice, but not in the rats, from 24 to 72 h or in either species dosed in drinking water. A significant elevation in the LI in response to furan treatment was detected in mice regardless of the route of BrdU administration. In furan-treated rats, the minipump-dosed group and the singly housed, but not the multiply housed water-dosed group, showed a significant increase in the BrdU LI in response to furan treatment. While the data from control mice and rats receiving BrdU by dosed water over a 3-day period did not show expected dose and time effects, this route was effective in detecting the elevated hepatocyte LI induced by treatment with furan. Since this study suggests the possibility of toxicity due to BrdU administration, additional lower-dose studies with the drinking water route of BrdU administration are needed before definitive recommendations can be made.