Vegesna V, Withers H R
Department of Radiation Oncology, UCLA 90024-1714.
Int J Radiat Oncol Biol Phys. 1991 May;20(5):997-1000. doi: 10.1016/0360-3016(91)90196-b.
A range of drug doses of Adriamycin (ADR), Actinomycin-D (ACT-D), and Mitomycin-C (MMC) were given i.v. or i.p. to mice 1 day after a priming dose of radiation to elicit epilation response. The hair follicles were stimulated through plucking 11 days before irradiation or were unstimulated to represent proliferating and nonproliferating populations. The maximum epilation that appears at 8 days or at 8.5 weeks for proliferating and nonproliferating follicles was quantified using a subjective scale. In general, the i.v. route of administration was more effective than i.p. for all three drugs. Proliferating follicles were more susceptible than non-proliferating follicles to the action of drugs, especially ADR (p = .0001). Radiation doses which would give the same effect as ADR were calculated for proliferating follicles: 8 mg/kg given i.v. was equivalent to 4.6 (3.9, 5.2) Gy. For i.p. administration, 8 mg/kg was equivalent to only 0.6 (-0.1, 1.3) Gy. The in vivo assay of drug effect on hair follicles has advantages over LD10 as a model for toxicological investigation of new drugs: it can assess response of proliferating or non-proliferating cells of the same histotype and, in the case of proliferating follicles, it is quicker, thus enabling the use of doses higher than LD50 for bone marrow deaths.
在给予小鼠一次预照射剂量1天后，经静脉注射或腹腔注射给予一系列剂量的阿霉素（ADR）、放线菌素-D（ACT-D）和丝裂霉素-C（MMC），以引发脱毛反应。在照射前11天通过拔毛刺激毛囊，或者不进行刺激以代表增殖和非增殖群体。使用主观评分法对增殖和非增殖毛囊在8天或8.5周时出现的最大脱毛情况进行量化。一般来说，对于这三种药物，静脉注射给药途径比腹腔注射更有效。增殖毛囊比非增殖毛囊对药物作用更敏感，尤其是阿霉素（p = 0.0001）。计算了对增殖毛囊产生与阿霉素相同效果的辐射剂量：静脉注射8 mg/kg相当于4.6（3.9, 5.2）Gy。对于腹腔注射，8 mg/kg仅相当于0.6（-0.1, 1.3）Gy。药物对毛囊作用的体内试验作为一种新药毒理学研究模型，比LD10具有优势：它可以评估同一组织类型的增殖或非增殖细胞的反应，并且对于增殖毛囊而言，速度更快，因此能够使用高于骨髓致死LD50的剂量。
