Hopkins H A, Looney W B, Teja K, Hobson A S, MacLeod M S
Br J Cancer. 1978 Jun;37(6):1006-14. doi: 10.1038/bjc.1978.146.
The effects of adriamycin (Adr) on the solid-tumour model, hepatoma 3924A, and on critical organs of the host, were determined at intervals after single injections of 60 mg/m2 of the agent. A reduced rate of tumour growth was evident 4 days after treatment, continued to Day 11, and then returned to rates comparable to control values. On Day 11 tumour volumes of treated animals were 38% of control. During the period of reduced growth, 3H-TdR incorporation into tumour DNA and percentage labelled tumour cells were less than control values. DNA concentration in tumour was not affected by drug treatment, which differs from observations made in other studies employing 5-fluorouracil (FU). No evidence of significantly increased necrosis or fibrosis of the tumour was found after Adr. The Adr treatment caused loss of 60% of the tibial marrow by Day 4, as measured by total DNA content. Marrow DNA recovered to control levels between Days 7 and 11. Incorporation of 3H-TdR into heart DNA was reduced more than 40% during the first week after Adr treatment; enhanced incorporation was observed on Day 11, and control levels were attained by Day 17. No significant pathological evidence of cardiac toxicity was found 2-21 days after Adr but degeneration of myocardial cells and oedema was prominent at 14 weeks.
单次注射60mg/m²阿霉素(Adr)后,定期测定其对实体瘤模型肝癌3924A以及宿主关键器官的影响。治疗后4天肿瘤生长速率明显降低,持续至第11天,然后恢复至与对照值相当的速率。在第11天,治疗组动物的肿瘤体积为对照组的38%。在生长速率降低期间,肿瘤DNA中³H-TdR掺入量和标记肿瘤细胞百分比均低于对照值。肿瘤中的DNA浓度不受药物治疗影响,这与使用5-氟尿嘧啶(FU)的其他研究结果不同。阿霉素治疗后未发现肿瘤坏死或纤维化显著增加的证据。以总DNA含量衡量,阿霉素治疗在第4天时导致胫骨骨髓损失60%。骨髓DNA在第7天至第11天恢复至对照水平。阿霉素治疗后第一周内心脏DNA中³H-TdR掺入量减少超过40%;在第11天观察到掺入量增加,到第17天达到对照水平。阿霉素治疗后2至21天未发现明显的心脏毒性病理证据,但在14周时心肌细胞变性和水肿明显。