Activity of thymidine as a chemotherapeutic agent against human tumor xenografts in nude mice

Abstract

The chemotherapeutic activity of thymidine (dThd) was tested against four human tumor xenografts growing in nude mice, including a melanoma, an oat cell carcinoma of the lung, a colon carcinoma, and a breast carcinoma. Tumor-bearing mice were given an infusion of dThd (1 g/kg/day) s.c. for 72 hr each week for three weeks. Tumor growth in the treated mice was compared to that in randomized concurrent control mice infused with media alone. A significant effect was found only for the melanoma, and it was cytostatic rather than cytotoxic. Even when melanomas of very small initial volume were treated, there were no complete regressions, and tumor growth resumed when dThd treatment was stopped. In culture, sustained dThd concentrations of greater than 3.2 mM were required to cause death of the melanoma cells; in the mice the dThd level during infusion ranged from 1 to 5 mM. This exposure to dThd, although failing to produce a tumor response, did produce significant toxicity in the nude mice in the form of myelosuppression and leukopenia. Flow cytometric analysis of marrow cells during the dThd infusion showed an accumulation of cells in S phase, but proliferation was not completely halted since cells with G2-M content of DNA were present in the marrow even after 72 hr of dThd exposure. This study failed to demonstrate a therapeutically useful effect of dThd on these tumors.