MEASUREMENT OF REPLICATIVE DNA-SYNTHESIS (RDS) BY A 5-BROMO-2'-DEOXYURIDINE (BRDU) LABELING TECHNIQUE FOR DETECTION OF HEPATOCYTE PROLIFERATION

The hypothesis has been proposed that cell proliferation, or replicati ve DNA synthesis (RDS) in S-phase cells, is a nongenotoxic (Ames-negat ive) mechanism involved in tumorigenesis, providing a very useful conc eptual basis for carcinogen testing. In this present study, hepatocyte RDS experiments were conducted using 5-bromo-2'-deoxyuridine (BrdU) l abeling in combination with histopathological observation, comparing o ur results with earlier findings for in situ [H-3]thymidine (TdR) labe ling. The present BrdU data proved to be consistent with the previous TdR data in all but one case. Hepatocyte RDS induction was observed fo r some chemicals without hepatotoxicity. BrdU labeling in combination with histopathological observation is therefore a reliable approach to assessment of test compound effects in vivo.