Enhancement of experimental metastasis by pretreatment of tumour cells with hydroxyurea

Abstract

The effect of treatment with hydroxyurea (HU), on subsequent experimental metastasis formation by cells of 3 murine melanoma lines has been examined. In vitro treatment of B16‐F1, B16‐F10and K‐1735‐clone 19 cells with 0.1 mM or 0.3mM HU, followed by a period of recovery in drug‐free medium, resulted in a significant increase in the number of lung nodules formed in syngeneic mice following i.v. injection of the cells. The maximum effect obtained was observed when cells were injected 6 hr after removal of HU and it occurred in spite of the cytotoxicity of the doses used. Six hours after release from treatment with 0.3 mM HU cells were synchronized in the G₂ phase of the cell cycle but the consequent increase in cell volume was not responsible for increased metastasis through enhancement of tumour‐cell arrest, since lodgement of ⁵¹Cr‐labelled, HU‐treated cells was no greater than that of control cells. The results obtained suggest that the chemotherapeutic agent HU may facilitate tumour progression via a direct action on neoplastic cells.