Measurement of replicative DNA synthesis (RDS) by a 5-bromo-2'-deoxyuridine (BrdU) labeling technique for detection of hepatocyte proliferation.

ABSTRACT

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