Creveling C R, Kirk K L, Highman B
Res Commun Chem Pathol Pharmacol. 1977 Mar;16(3):507-22.
Administrationof L-2-fluorohistidine to mice produces a dose and time dependent leukopenia, hypocellularity with reduction in hematopoiesis in the spleen and bone marrow, and depletion of lymphocytes in the spleen, lymph nodes and cortex of the thymus. The LD50 is 250 mg/kg at five days. The effect on hematopoetic tissue is nearly as great at non-leathal "therapeutic" doses. Effects on circulating erythrocyte and reticulocyte levels and the deposition of hemosiderin in the spleen are minimal. At non-leathal doses the effects of this amino acid analog appear to be completely reversible after 6 to 10 days.A description of the toxicity, histopathology and a discussion of the possible mechanisms of action are presented.
给小鼠注射L-2-氟组氨酸会产生剂量和时间依赖性的白细胞减少、细胞减少,脾脏和骨髓造血功能降低,以及脾脏、淋巴结和胸腺皮质中的淋巴细胞耗竭。五天时的半数致死剂量(LD50)为250毫克/千克。在非致死性“治疗”剂量下,对造血组织的影响几乎同样显著。对循环红细胞和网织红细胞水平以及脾脏中含铁血黄素沉积的影响最小。在非致死剂量下,这种氨基酸类似物的作用在6至10天后似乎完全可逆。本文介绍了其毒性、组织病理学并讨论了可能的作用机制。