Transient induction of single GST-P positive hepatocytes by DEN.
Transient induction of single GST-P positive hepatocytes by DEN.
复制标题
DEN 瞬时诱导单个 GST-P 阳性肝细胞。
作者：
K. Satoh;I. Hatayama;N. Tateoka;K. Tamai;T. Shimizu;M. Tatematsu;N. Ito;K. Sato
胎盘谷胱甘肽S转移酶(GST-P)阳性的单个细胞，在用肝癌药物治疗后不久在大鼠的肝脏中检测到，可能是“起始细胞”，这一假说在本系列实验中得到了验证。雄性SD大鼠在不同单次剂量的二乙基亚硝胺(DEN)作用下未观察到低剂量阈值，但在160~200 mg/kg体重范围内达到平台值。单次给药1周后，大鼠肝脏免疫组织化学阳性细胞数约为12,400个/cm~3，8周后下降，之后又回升。早期以单细胞为主，但随着时间的推移，微小病灶和较大病变逐渐增多。单次DEN治疗后2~24周，给大鼠施加选择性压力(含0.02%2-AAF饲料加肝部分切除)，可形成GST-P阳性的大病灶，尤其是在早期，生长反应随时间延长而不明显。另一方面，病灶的数量与在同一个体的肝切除组织中检测到的单细胞/小病灶的数量相关。这些结果提示，早期GST-P阳性人群可能是癌前病变和结节的先兆。
The single cells positive for placental glutathione S-transferase (GST-P), detectable in livers of rats soon after treatment with hepatocarcinogens, are possible 'initiated cells', the hypothesis tested in the present series of experiments. No low dose threshold was observed in male Sprague-Dawley rats at different single doses of diethylnitrosamine (DEN) although a plateau was reached between 160 and 200 mg/kg body weight. At the latter single dose approximately 12,400 positive cells/cm3 were observed immunohistochemically in rat livers after one week, the numbers then decreasing to week 8 and thereafter rising again. In the early stages single cells predominated but with time a gradual increase in mini-foci and larger lesions became evident. Application of selection pressure (feeding of diet containing 0.02% 2-AAF plus partial hepatectomy) to rats 2-24 weeks after single DEN-treatment resulted in the formation of large foci positive for GST-P, especially in the early stages, the growth response being less pronounced with time. The number of foci, on the other hand, was correlated with the number of single cells/mini-foci detected in hepatectomy tissue of the same individuals. These results suggest that the early GST-P positive populations could be the precursor for preneoplastic foci and nodules.