Different effects of L-histidinol and homoharringtonine on 5-fluorouracil and bis-chloroethylnitrosourea activity in a murine model

Abstract A comparison of the effects of L-histidinol and homoharringtonine (HHT) on the activity of 5-fluorouracil (FUra) and bis-chloroehtylnitrosourea (BCNU) in C57/BL mice, without or with disseminated B16f10 melanoma, was carried out. Although L-histidinol and HHT are both protein synthesis inhibitors with apparently identical modes of action, these two compounds had very different effects in the test systems. HHT failed to prevent the body weight lose and subsequent death of C57/BL mice treated with supralethal doses of FUra; it was also unable to prevent the toxicity of FUra for bone marrow cells. In contrast, L-histidinol prevented the weight loss, death and bone marrow damage otherwise resulting from identical doses of FUra. Furthermore, L-histidinol was far more effective than HHT in its ability to improve the management of disseminated B16f10 melanoma in C57/BL mice by BCNU, both in terms of reducing pulmonary foci and extending survival.