Coni P, Pichiri-Coni G, Curto M, Simbula G, Giacomini L, Sarma D S, Ledda-Columbano G M, Columbano A
Istituto di Patologia Sperimentale, University of Cagliari, Italy.
Jpn J Cancer Res. 1993 May;84(5):501-7. doi: 10.1111/j.1349-7006.1993.tb00167.x.
The possible mechanism(s) responsible for the different effects exerted by proliferative stimuli of different nature on the appearance of enzyme-altered hepatic foci, were investigated in male Wistar rats. Rats given an initiating dose of diethylnitrosamine (150 mg/kg body weight) were fed a diet containing 0.03% acetylaminofluorene for 2 weeks. Between the first and the second week, cell proliferation was induced by a proliferative stimulus of compensatory type (partial hepatectomy) or by a direct mitogenic stimulus (lead nitrate, 100 mumol/kg). The effect of the two different proliferative stimuli on the appearance of gamma-glutamyl transferase-positive foci was monitored by killing the rats for examination at 1, 2, 3, 5, and 6 days after the induction of cell proliferation. The results indicate that while enzyme-altered hepatocytes can be observed as early as 3 days after partial hepatectomy and are characterized by a rapid growth, direct hyperplasia did not exert any effect on the growth capacity of initiated cells. No effect of lead nitrate-induced hyperplasia was observed following three administrations of the mitogen. When platelet-poor plasma taken from animals exposed to the different proliferative stimuli was tested in primary cultures of hepatocytes, it was found that it induced a significant increase in the labeling index of normal hepatocytes. However, while serum taken 6 days after partial hepatectomy was still able to induce a significant increase in the labeling index, platelet-poor plasma from lead-treated rats had lost part of its effect at 5 days after treatment. The inability of direct hyperplasia to stimulate the development of enzyme-altered hepatic foci was not unique to lead nitrate since the same phenomenon was observed when three other hepatomitogens, nafenopin, cyproterone acetate, and ethylene dibromide, were used.
在雄性Wistar大鼠中，研究了不同性质的增殖刺激对酶改变的肝病灶出现产生不同影响的可能机制。给大鼠给予二乙基亚硝胺起始剂量（150mg/kg体重），并喂食含0.03%乙酰氨基芴的饮食2周。在第一周和第二周之间，通过代偿性增殖刺激（部分肝切除术）或直接促有丝分裂刺激（硝酸铅，100μmol/kg）诱导细胞增殖。通过在细胞增殖诱导后1、2、3、5和6天处死大鼠进行检查，监测两种不同增殖刺激对γ-谷氨酰转移酶阳性病灶出现的影响。结果表明，虽然在部分肝切除术后3天就可观察到酶改变的肝细胞，且其特点是快速生长，但直接增生对起始细胞的生长能力没有任何影响。在给予三次促有丝分裂原后，未观察到硝酸铅诱导的增生有任何作用。当在肝细胞原代培养中测试从接受不同增殖刺激的动物中获取的贫血小板血浆时，发现它可诱导正常肝细胞的标记指数显著增加。然而，虽然部分肝切除术后6天采集的血清仍能诱导标记指数显著增加，但铅处理大鼠的贫血小板血浆在处理后5天已失去部分作用。直接增生不能刺激酶改变的肝病灶发展并非硝酸铅所特有，因为当使用其他三种肝促有丝分裂原，即萘夫平、醋酸环丙孕酮和1,2-二溴乙烷时，也观察到了相同的现象。
