van Hoesel Q G, Steerenberg P A, Vos J G, Hillen F C, Dormans J A
J Natl Cancer Inst. 1984 May;72(5):1141-50.
Antitumor activity, cardiotoxicity, and nephrotoxicity induced by doxorubicin were studied in LOU/M/WSL inbred rats each bearing a transplantable solid IgM immunocytoma. Animals with a tumor (diameter, 15.8 +/- 3.3 mm) were treated with iv injections of doxorubicin on 5 consecutive days, followed by 1 weekly injection for 7 weeks (dose range, 0.015-4.0 mg/kg body wt). Tumor regression was observed with 0.5 mg doxorubicin/kg. Complete disappearance of the tumor was induced with 1.0 mg doxorubicin/kg. Histologic evidence of cardiotoxicity scored as grade III was only observed at a dose of 1.0 mg doxorubicin/kg. Light microscopic evidence of renal damage was seen above a dose of 0.5 mg doxorubicin/kg, which resulted in albuminuria and very low serum albumin levels. In the group that received 1.0 mg doxorubicin/kg, the serum albumin level decreased from 33.6 +/- 4.1 to 1.5 +/- 0.5 g/liter. Ascites and hydrothorax were observed simultaneously. The same experiments were performed with non-tumor-bearing rats, in which no major differences were observed. In conclusion, antitumor activity, cardiotoxicity, and nephrotoxicity were studied simultaneously in the same LOU/M/WSL rat. Albuminuria due to renal damage led to extremely low serum albumin levels, so ascites and hydrothorax were not necessarily a consequence of the observed cardiomyopathy.
在每只携带可移植实体IgM免疫细胞瘤的LOU/M/WSL近交系大鼠中，研究了阿霉素诱导的抗肿瘤活性、心脏毒性和肾毒性。对肿瘤直径为15.8±3.3毫米的动物连续5天静脉注射阿霉素，随后每周注射1次，共7周（剂量范围为0.015 - 4.0毫克/千克体重）。观察到0.5毫克阿霉素/千克可使肿瘤消退。1.0毫克阿霉素/千克可使肿瘤完全消失。仅在剂量为1.0毫克阿霉素/千克时观察到组织学证据显示心脏毒性评分为III级。在剂量高于0.5毫克阿霉素/千克时可见肾脏损害的光镜证据，这导致蛋白尿和血清白蛋白水平极低。在接受1.0毫克阿霉素/千克的组中，血清白蛋白水平从33.6±4.1降至1.5±0.5克/升。同时观察到腹水和胸腔积液。对无肿瘤大鼠进行了相同的实验，未观察到重大差异。总之，在同一LOU/M/WSL大鼠中同时研究了抗肿瘤活性、心脏毒性和肾毒性。肾脏损害导致的蛋白尿导致血清白蛋白水平极低，因此腹水和胸腔积液不一定是所观察到的心肌病的结果。
