Changes in 2′-deoxycytidine levels in various tissues of tumor-bearing mice

Abstract

The nucleoside 2'-deoxycytidine (dCyd) increases in the plasma of cancer patients with poor prognoses. 5-fluorouracil (5FU) is one of the anti-cancer agents used in chemotherapy for patients whose plasma dCyd is elevated. We examined the free dCyd level in various tissues of mice, with and without tumors, and in mice with and without the administration of 5FU or of dCyd, and investigated the effects of dCyd in tumor-bearing animals. SP2/0-Ag14 mouse myeloma cells were transplanted subcutaneously into mice and 5FU or dCyd was administered intraperitoneally. Free dCyd was measured in blood and tissues by HPLC at two time points, once when mouse body weight was maximally decreased (1 day after the last administration of 5FU, day 16) and again when it returned to control level at 1 week after the last 5FU treatment (day 22). Results showed that in tumor-bearing mice, the level of dCyd (per g wet weight) increased in the spleen. The change in liver weight caused by the administration of 5FU correlated with the level of dCyd in the liver. Notably, the relative tumor volume and tumor weight was decreased in dCyd-treated animals in comparison with controls. In conclusion, the levels of dCyd were markedly altered in the tissues of the reticuloendothelial and lymphatic systems, such as liver and spleen, and dCyd apparently had the ability to inhibit tumor growth in the body.