Kaufmann W K, Zhang Y, Kaufman D G
Department of Pathology, University of North Carolina, Chapel Hill 27599.
Carcinogenesis. 1992 Apr;13(4):703-7. doi: 10.1093/carcin/13.4.703.
The antitumor antibiotic, bleomycin, was tested for activity as an initiator of hepatocellular foci and neoplasms in rats. The compound was administered in a single dose via the portal vein 4 h after the proliferative stimulus of a two-thirds partial hepatectomy. Rats were subsequently fed diet containing phenobarbital for up to 41 weeks to promote the development of initiated hepatocytes. Bleomycin-treated livers displayed significantly increased frequencies of basophilic hepatocellular foci and hepatocellular foci which retain glycogen during fasting. Foci that express glutathione-S-transferase (placental form) were not initiated by bleomycin. Hepatocellular neoplasms were infrequently seen in bleomycin-treated livers (5% incidence). The results suggest that oxygen radical-mediated DNA damage may initiate, within populations of proliferating hepatocytes, new lineages of altered hepatocytes that form foci but have low probability of progressing to neoplasms during promotion with phenobarbital.
对抗肿瘤抗生素博来霉素进行了测试，以检验其作为大鼠肝细胞灶和肿瘤引发剂的活性。在三分之二部分肝切除的增殖刺激4小时后，通过门静脉给予该化合物单剂量。随后，给大鼠喂食含苯巴比妥的饲料长达41周，以促进起始肝细胞的发育。经博来霉素处理的肝脏中，嗜碱性肝细胞灶和禁食期间保留糖原的肝细胞灶的频率显著增加。表达谷胱甘肽-S-转移酶（胎盘型）的灶不是由博来霉素引发的。在经博来霉素处理的肝脏中很少见到肝细胞肿瘤（发生率为5%）。结果表明，氧自由基介导的DNA损伤可能在增殖的肝细胞群体中引发新的改变的肝细胞谱系，这些肝细胞形成病灶，但在用苯巴比妥促进过程中发展为肿瘤的可能性较低。
