Haese W H, Bueding E
J Pharmacol Exp Ther. 1976 Jun;197(3):703-13.
In confirmation of an earlier study, it was found that in mice infected with Schistosoma mansoni hepatocellular carcinomas are induced by hycanthone, an antischistosomal drug and potent frameshift mutagen. In addition, a high incidence 1) of micronodular hepatocellular whirling lesions with increased basophilia, 2) of other proliferative areas of altered cellularity and 3) of precancerous nodules was found in the livers of schistosome-infected mice treated with hycanthone. A dosage schedule of hycanthone which was too small to have any significant chemotherapeutic effect in mice (3 X 3 mg/kg) was sufficient to induce a statistically highly significant incidence of micronodular lesions and of precancerous nodules. Hence, the hepatic tissue proved more susceptible to low doses of this drug than the parasite. No significant hepatocarcinogenic effects or other hepatocellular changes were induced by chemotherapeutically effective doses of two related equipotent antischistosomal compounds, a chloroindazole analog of hycanthone, IA-4, and the tetrahydroquinoline derivative, oxamniquine.
正如早期研究所证实的那样，发现感染曼氏血吸虫的小鼠中，抗血吸虫药物且具有强大移码诱变作用的海恩酮可诱发肝细胞癌。此外，在用海恩酮治疗的血吸虫感染小鼠肝脏中，发现了1）嗜碱性增强的微小结节性肝细胞漩涡状病变、2）细胞数量改变的其他增殖区域以及3）癌前结节的高发生率。在小鼠体内，一个对化疗没有任何显著效果的海恩酮剂量方案（3×3毫克/千克）足以诱导微小结节病变和癌前结节的发生率在统计学上具有高度显著性。因此，肝脏组织被证明比寄生虫对这种药物的低剂量更敏感。两种相关的等效抗血吸虫化合物，海恩酮的氯吲唑类似物IA - 4和四氢喹啉衍生物奥沙尼喹，其化疗有效剂量未诱导出显著的致癌作用或其他肝细胞变化。
