Rao M S, Subbarao V
Department of Pathology, Northwestern University Medical School, Chicago, IL 60611, USA.
Cancer Lett. 1995 Nov 6;97(2):185-8. doi: 10.1016/0304-3835(95)03975-3.
It is hypothesized that hepatic tumors in rats induced by peroxisome proliferators is dependent on peroxisome proliferative effect of these compounds and the resulting oxidative stress. However, it is argued that since these compounds also induce tumors in pancreas and testes, the two organs in which there is no proliferation of peroxisomes, the carcinogenic effect is unlikely to be related to oxidative stress. To clarify this controversy we have systematically analyzed the incidence of pancreatic acinar cell foci and nodules, and testicular Leydig cell tumors in ciprofibrate treated and control rats. In animals treated with 0.025% ciprofibrate for 22 months the incidence of Leydig cell tumors and acinar cell lesions was 100% and 66%, respectively. In age-matched controls the incidence of testicular and pancreatic lesions was 93% and 66%, respectively. These findings clearly demonstrate that the Leydig cell tumors and pancreatic lesions develop spontaneously and are not induced by ciprofibrate.
据推测，过氧化物酶体增殖剂诱导的大鼠肝脏肿瘤依赖于这些化合物的过氧化物酶体增殖效应以及由此产生的氧化应激。然而，有人认为，由于这些化合物也会在胰腺和睾丸中诱发肿瘤，而这两个器官中不存在过氧化物酶体的增殖，所以致癌作用不太可能与氧化应激有关。为了澄清这一争议，我们系统地分析了环丙贝特处理组和对照组大鼠胰腺腺泡细胞灶和结节以及睾丸间质细胞瘤的发生率。在用0.025%环丙贝特处理22个月的动物中，间质细胞瘤和腺泡细胞病变的发生率分别为100%和66%。在年龄匹配的对照组中，睾丸和胰腺病变的发生率分别为93%和66%。这些发现清楚地表明，间质细胞瘤和胰腺病变是自发产生的，而非环丙贝特所诱发。
