CELL-PROLIFERATION RATES IN COMMON CANCER TARGET TISSUES OF B6C3F1 MICE AND F344 RATS - EFFECTS OF AGE, GENDER, AND CHOICE OF MARKER

Increasing emphasis is being placed on mode of action for chemical car cinogens as an important consideration for risk assessment. Many roden t carcinogens appear to act through nongenotoxic mechanisms, such as i nduced cell proliferation. Information on cell proliferation rates bas ed on species, age, gender, tissue, and choice of marker will provide a foundation for incorporating such measurements into rodent toxicity studies. Cell proliferation was evaluated in liver, kidney, skin, and forestomach of control male and female B6C3F1 mice and F344 rats at 7, 10, 13, and 20 weeks of age. Proliferating cell nuclear antigen (PCNA ), an endogenous cell proliferation marker, and bromodeoxyuridine (Brd U) administered by ip injection 2 hr before euthanization were compare d as markers of cell proliferation. Only in liver were BrdU and PCNA l abeling indices (LIs; 3 phase only) statistically similar. As expected , the PCNA proliferating index (PI; G(1) + S + G(2) + M phases) was co nsistently greater than the 3 phase LI in all tissues examined. Age-re lated differences in LI were evident in liver and kidney, whereas LIs in the forestomach and skin were not age-dependent. In all tissues exa mined, gender- and species-related differences in cell proliferation w ere detected. Although BrdU and PCNA LIs were often statistically diff erent, they both provided a useful indication of cell proliferation ra tes in the tissues examined. These results provide potentially useful information for designing rodent toxicity studies and biological model s of carcinogenesis. (C) 1996 Society of Toxicology