L-histidinol inhibition of the proliferation and DNA biosynthesis of Ehrlich ascites carcinoma in vivo

ABSTRACT

L-histidinol, a structural analogue of the essential amino acid L-histidine, has been demonstrated to improve the selectivity and efficacy of a variety of cancer drug in several transplantable tumors. L-histidinol causes a rapid decrease in the incorporation of labeled thymidine into Ehrlich ascites carcinoma [EAC] tumor cells. The effect is expressed during 24 hours after L-histidinol treatment [250 mg/kg, 5 doses i.p., 2 hours apart] of EAC-bearing mice. The observed reduced incorporation of labeled thymidine is due to an inhibition of DNA biosynthesis. DNA synthesis was measured by an isotope dilution assay after pulse-labeling with [3H] thymidine 1 muCi/mouse and by monitoring the increase in the total amount of DNA of cell population. The data demonstrated that L-histidinol inhibits DNA biosynthesis and cell proliferation of Ehrlich ascites carcinoma in vivo