The natural history and dose-response characteristics of enzyme-altered foci in rat liver following phenobarbital and diethylnitrosamine administration.
The natural history and dose-response characteristics of enzyme-altered foci in rat liver following phenobarbital and diethylnitrosamine administration.
复制标题
苯巴比妥和二乙基亚硝胺给药后大鼠肝脏酶改变病灶的自然史和剂量反应特征。
DOI：
10.1093/carcin/5.1.67
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发表时间：
1984
期刊：
影响因子：
4.7
通讯作者：
Pitot,HC
中科院分区：
文献类型：
--
作者：
Goldsworthy,T;Campbell,HA;Pitot,HC
用70°部分肝切除术（PH）诱导雌性大鼠肝酶改变灶（EAF），然后单次灌胃给予二乙基亚硝胺（DEN）10 mg/kg。研究了这些病灶对不同剂量的促肝剂苯巴比妥（PB）的稳定性和反应。当给予促进剂后6个月不含PB的饮食时，PH/DEN后给予PB（0.05%）1周、2周、1个月、2个月、3个月或4个月导致的γ谷氨酰转肽酶阳性（GGT+）EAF的数量没有显著变化。这些数据证明了PH/DEN/PB方案诱导的fwi的稳定性，并表明在没有明显肝坏死的情况下，PB促进引起的病灶数量增加在去除促进刺激物后是不可逆的。在饲料中长期给予低于0.001%的PB剂量水平，未能证明EAF数量比未用PB促进的对照动物的数量增加。当大鼠在饮食中长期喂食0.001%至0.05%剂量的PB时，观察到EAF数量的线性增加，而PB > 0.05%的饮食浓度不会导致EM数量的任何进一步增加。在推广的前3-4个月期间，由PH/DEN随后在饮食中添加0.05%PB引起的EAF的数量增加。此后，尽管持续给予PB长达8个月，但病灶数量未发生变化。这些数据表明PB促进存在明显的阈值（无作用水平），并证明EAF在单剂量DEN启动后对该促进剂存在最大反应。
Enzyme-altered foci (EAF) were induced in the Liver of female rats by 70° partial hepatectomy (PH), followed by a single intragastric administration of diethylnitrosamine (DEN) at a dose of 10 mg/kg. The stability and response of these foci to various doses of the hepatic promoting agent, phenobarbital (PB), were studied. The number of yglutamyltranspeptidasepositive (GGT+) EAF resulting from PH/DEN followed by PB (0.05%) administration for 1 week, 2 weeks, 1 month, 2 months, 3 months or 4 months did not significantly change when the administration of the promoting agent was followed by a 6-month period of a diet containing no PB. These data demonstrate the stability of the fwi induced by the PH/DEN/PB regimen and indicate that the increased number of foci resulting from PB promotion in the absence of overt hepatic necrosis are not reversible on removal of the promoting stimulus. Chronic administration of dose levels of PB below 0.001% in the diet failed to demonstrate an increase in the number of EAF over the number in the control animals not promoted with PB. A linear increase in the number of EAF was observed when rats were chronically fed doses of PB ranging between 0.001% and 0.05% in the diet, whereas diet concentrations of PB > 0.05% did not result in any further increase in the number of EM. The number of EAF resulting from PH/DEN followed by 0.05% PB in the diet increased during the first 3–4 months of promotion. Thereafter, the number of foci did not change despite the continued administration of PB for as long as 8 months. These data suggest the presence of an apparent threshold (no effect level) for promotion by PB and demonstrate the presence of a maximal response of EAF to this promoting agent after initiation by a single dose of DEN.