Expression of dutpase in normal and neoplastic human tissues

The dUTPase enzyme functions to hydrolyze dUTP to dUMP: effectively removing dUTP from the DNA biosynthetic pathway during replication and repair. Recent evidence suggests that elevated dUTPase levels in human tissues may play a protective role against chemotherapeutic agents such as FUdR which target /italicizede novo thymidylate biosynthesis. Thus, dUTPase levels in human tissues may be relevant to understanding the efficacy of agents that target this biochemical pathway as well as understanding its general role in nucleotide metabolism. dUTPase monoclonal antibodies and an immunohistochemical technique were used to probe normal and neoplastic human tissues. In a survey of normal tissues, the dUTPase antibodies consistently labeled the nuclei of proliferative cells such as lyrnphoid germinal center B-cells and the basal layer of tonsil and skin epithelium; resembling the pattern of the clinical proliferation marker Ki67. An analysis of a range of human tumors revealed that nuclear dUTPase correlated with Ki67 staining. An extensive screening of dUTPase in a variety of human tumors is underway to assess its potential roîe as a prognostic marker.