DNA-synthesizing enzyme activities and the immunohistochemistry in proliferation of bone marrow cells in rats]

Thymidylate synthetase (TS) and thymidine kinase (TK) are know to catalyze the methylation of dUMP for the de novo synthesis of dTMP and the phosphorylation of thymidine for the salvage synthesis of dTMP in the pyrimidine pathway, respectively, and both enzyme activities are high in rapidly proliferating tissues. In the present study, these enzyme activities and the immunohistochemistry using monoclonal anti-bromodeoxyuridine (BrdU) were investigated during the period of proliferation of bone marrow cells after the hypoplastic period induced by cyclophosphamide (Cy) treatment in rats. Right after Cy treatment, nucleated cell count (NCC) of bone marrow cells, BrdU labelling ratio and TK activity were abruptly decreased. On the other hand, TS activity peaked at day 5 followed by an increase of TK activity, NCC and BrdU labelling ratio from day 7 after Cy treatment. These results indicate that, in the proliferation of bone marrow cells, the DNA de novo synthesis rises at first, and secondly, the DNA salvage synthesis predominantly increases with the increase of bone marrow cells labelled with BrdU, i.e., increase of the cells in the S phase.