Further evidence that mitogen-induced cell proliferation does not support the formation of enzyme-altered islands in rat liver by carcinogens.
Further evidence that mitogen-induced cell proliferation does not support the formation of enzyme-altered islands in rat liver by carcinogens.
复制标题
进一步的证据表明，丝裂原诱导的细胞增殖并不支持致癌物在大鼠肝脏中形成酶改变岛。
DOI：
10.1093/carcin/10.5.847
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发表时间：
1989
期刊：
影响因子：
4.7
通讯作者：
Pani,P
中科院分区：
文献类型：
--
作者：
Ledda-Columbano,GM;Columbano,A;Curto,M;Ennas,MG;Coni,P;Sarma,DS;Pani,P
Our earlier studies have revealed that direct hyperplasia induced by liver mitogens such as lead nitrate, ethylene dibromide, nafenopin and cyproterone acetate, unlike compensatory cell proliferation induced by partial hepatectomy and CCI4, does not support the formation of enzyme-altered islands induced by chemical carcinogens in the liver. In the previous studies carcinogens were given at the peak of DNA synthesis induced by the liver mitogens. If the mitogens have altered the sensitive phase of the hepatocyte to the carcinogenic attack, administering the carcinogen at one time point following the mitogenic stimulus might have missed the sensitive phase. In order to overcome this possibility in the present study male Wistar rats weighing 200–250 g were givenN-methyl-N-nitrosourea (MNU; 60 mg/kg, i.p.) at three points representing G1, S and G2/M phases of the cell cycle following different types of liver cell proliferative stimuli. In another experiment MNU (60 mg/kg, i.p.) and diethylnitrosamine (15 mg/kg, i.p.) were given prior to the administration of proliferative stimuli. The initiated hepatocytes were also assayed following promotion by two different promoting regimens, namely phenobarbital and the resistant-hepatocyte model. Further, the initiated hepatocytes were monitored not only by using the appearance of islands of enzyme-altered hepatocytes but also using the incidence of hepatocellular carcinoma. The results of this study clearly revealed that irrespective of the protocol used, only the compensatory liver cell proliferation but not the mitogen-induced direct hyperplasia supported the formation and the growth of enzyme-altered islands in the liver induced by chemical carcinogens.
