Milligan A J, Katz H R, Leeper D B
J Natl Cancer Inst. 1978 May;60(5):1023-8. doi: 10.1093/jnci/60.5.1023.
A sublethal dose of 100 mg lucanthone hydrochioride/kg (Miracil D, Nilodin; NSC-14574) administered ip into Chinese hamsters [median lethal dose for 30-day survival (LD50/30) of 315 mg/kg] reduced the radiation tolerance of the small intestine and had little or no effect on the radiation tolerance of the bone marrow. Lucanthone hydrochloride was administered at various times before and after whole-body 60Co gamma-irradiation. The median lethal dose for 7-day survival (LD50/7), indicative of death from gastrointestinal epithelial denudation, was reduced from 1,235 rads to minimum values of 995 rads or 985 rads by lucanthone hydrochloride inoculation 10 hours before irradiation or 7.5 hours post irradiation, respectively. The LD50/30, indicative of death from bone marrow stem cell depletion, remained unaltered at approximately 990 rads over the entire treatment scheme, which indicated that the radioresponsiveness of bone marrow stem cells was unaffected by lucanthone hydrochloride. The lucanthone hydrochloride effect was reversible in that control values of LD50/7 were attained by 40 hours post inoculation. Serum concentration of lucanthone hydrochloride in the Chinese hamster, determined spectrophotometrically, reached a peak of 8 microgram/ml by 1.5 hours post inoculation and then decreased exponentially with a half-life of approximately 6 hours, so that by 30 hours post inoculation it was unmeasurable.
以100毫克盐酸卢卡酮/千克(米拉西尔D、尼洛丁;NSC - 14574)的亚致死剂量腹腔注射给中国仓鼠[30天存活的半数致死剂量(LD50/30)为315毫克/千克],会降低小肠的辐射耐受性,而对骨髓的辐射耐受性几乎没有影响或没有影响。在全身60Coγ射线照射之前和之后的不同时间给予盐酸卢卡酮。7天存活的半数致死剂量(LD50/7),表明因胃肠道上皮剥脱而死亡,在照射前10小时或照射后7.5小时接种盐酸卢卡酮后,分别从1235拉德降至最低值995拉德或985拉德。LD50/30,表明因骨髓干细胞耗竭而死亡,在整个治疗方案中保持在约990拉德不变,这表明骨髓干细胞的放射反应性不受盐酸卢卡酮的影响。盐酸卢卡酮的作用是可逆的,因为接种后40小时达到了LD50/7的对照值。通过分光光度法测定,中国仓鼠血清中盐酸卢卡酮的浓度在接种后1.5小时达到峰值8微克/毫升,然后呈指数下降,半衰期约为6小时,因此接种后30小时无法测量。