Development of Cell Proliferation Assays in Rodents

Increasing evidence suggests that chemically-induced cell proliferation plays a role in carcinogenesis. The complex relationships between chemically-induced mutations, cytotoxicity, cell proliferation and carcinogenesis are important considerations in setting doses for cancer bioassays, classifying chemical carcinogens, and providing more realistic risk assessment approaches. Variables that might potentially influence chemically-induced cell proliferation include animal age, diet, chemical dose and treatment regimen, choice of cell proliferation marker, time and duration that the marker is administered, and quantitation methods. The quality, interpretation, and usefulness of chemically- induced cell proliferation data are dependent on the procedures and protocols used. The goal of this Phase I study is to quantitate background cell proliferation rates in selected target tissues from rodents of various ages. This study is designed to mimic conditions of a National Toxicology Program carcinogenicity bioassay. The results will be used to help establish appropriate cell labeling procedures that might be used in future cancer bioassays.