Watkins J R, Kim S N, Jayasekara U, Anderson J A, Fitzgerald J E, de la Iglesia F A
J Appl Toxicol. 1986 Feb;6(1):31-6. doi: 10.1002/jat.2550060107.
Ametantrone acetate (anthracenedione diacetate, NSC 287513) is an experimental antineoplastic agent with activity against a comprehensive panel of solid transplantable tumors in mice and dogs were carried out to establish tolerable levels. In mice, LD10, LD50 and LD90 values were respectively, 26, 35 and 47 mg kg-1 28 days following single intravenous injection and 22, 67 and 206 mg kg-1 14 days after single intraperitoneal injection. Hemorrhage and necrosis of the small intestine occurred in intercurrent deaths. A 5-day, consecutive intraperitoneal dosing study yielded 28 day, LD10, LD50 and LD90 values of 18, 21 and 26 mg kg-1, respectively, in mice. Bone marrow hypoplasia, lymphoid depletion and focal cardiac changes were observed in animals which died during the 28-day postdose observation period. In dogs, single intravenous injections repeated twice at intervals of 3-8 weeks resulted in leukopenia and thrombocytopenia at a dose of 2.71 mg kg-1 and decreased myeloid: erythroid ratios at a dose of 0.68 mg kg-1. Five consecutive daily intravenous injections in dogs of 0.7 mg kg-1 induced significant clinical and laboratory signs of toxicity but 0.35 mg kg-1 day-1 was tolerated. In dogs, bone marrow, lymphoid tissue and gastro-intestinal tract in both sexes and gonads in the males were target organs for toxicity. Clinical signs and clinical laboratory abnormalities abated in surviving mice and dogs. The spectrum of tissue changes induced by ametantrone was qualitatively similar to that elicited with other intercalating agents.
醋酸氨茴环素（蒽二酮二乙酸酯，NSC 287513）是一种实验性抗肿瘤药物，对小鼠和犬的多种可移植实体瘤具有活性。已开展相关研究以确定其可耐受水平。在小鼠中，单次静脉注射28天后，LD10、LD50和LD90值分别为26、35和47mg/kg；单次腹腔注射14天后，LD10、LD50和LD90值分别为22、67和206mg/kg。并发死亡的小鼠出现小肠出血和坏死。一项为期5天的连续腹腔给药研究得出，小鼠28天的LD10、LD50和LD90值分别为18、21和26mg/kg。在给药后28天的观察期内死亡的动物中，观察到骨髓发育不全、淋巴细胞耗竭和局灶性心脏改变。在犬中，每隔3 - 8周重复进行两次单次静脉注射，剂量为2.71mg/kg时会导致白细胞减少和血小板减少，剂量为0.68mg/kg时会导致髓系：红系比例降低。犬连续5天每天静脉注射0.7mg/kg会引发明显的临床和实验室毒性体征，但0.35mg/kg/天可耐受。在犬中，两性的骨髓、淋巴组织和胃肠道以及雄性的性腺是毒性靶器官。存活的小鼠和犬的临床体征和临床实验室异常情况有所减轻。氨茴环素诱导的组织变化谱在性质上与其他嵌入剂引起的相似。
