Tennekes H, van Ravenzwaay B, Kunz H W
Carcinogenesis. 1985 Oct;6(10):1457-62. doi: 10.1093/carcin/6.10.1457.
The dose-response characteristics of dieldrin-mediated enhancement of liver tumour formation in CF-1 mice were analysed, using existing tumour data from chronic feeding studies at six levels of continuous exposure, involving a total of greater than 1500 animals. The dose-response relationship can be expressed as: Dx X Tx = D0 X T0 = constant, where T0 = the median liver tumour induction period in control CF-1 mice, Tx = the median liver tumour induction period in dieldrin-treated mice at a dose level Dx, D0 = the background dose equivalent for the induction of 'spontaneous' liver tumours, Dx = the sum of background dose (D0) and actual dieldrin dose (delta x). The relationship, which is a Druckrey equation (D X Tn = constant) where n = 1, indicates that: (i) the velocity of liver tumour development is proportional to the daily dose level (Dx), (ii) the total tumourigenic dose is constant across all doses, (iii) the effects of dieldrin on the neoplastic process in mouse liver are essentially irreversible and cumulative, and (iv) there is no evidence for a threshold level. However, when delta x much less than D0, the actual contribution of dieldrin to tumour formation is expected to be negligible.
利用来自六个连续暴露水平的慢性喂养研究的现有肿瘤数据(涉及总共超过1500只动物),分析了狄氏剂介导的CF-1小鼠肝脏肿瘤形成增强的剂量反应特征。剂量反应关系可以表示为:Dx×Tx = D0×T0 =常数,其中T0 =对照CF-1小鼠的肝脏肿瘤诱导期中位数,Tx =在剂量水平Dx下经狄氏剂处理的小鼠的肝脏肿瘤诱导期中位数,D0 =诱导“自发”肝脏肿瘤的背景剂量当量,Dx =背景剂量(D0)与实际狄氏剂剂量(δx)之和。该关系是一个Druckrey方程(D×Tn =常数,其中n = 1),这表明:(i)肝脏肿瘤发展速度与每日剂量水平(Dx)成正比,(ii)所有剂量下的总致癌剂量是恒定的,(iii)狄氏剂对小鼠肝脏肿瘤形成过程的影响基本上是不可逆的且具有累积性,以及(iv)没有证据表明存在阈值水平。然而,当δx远小于D0时,预计狄氏剂对肿瘤形成的实际贡献可忽略不计。