Waddell William J
Department of Pharmacology and Toxicology, School of Medicine, University of Louisville, Louisville, KY, USA.
Hum Exp Toxicol. 2005 Jun;24(6):325-32. doi: 10.1191/0960327105ht525oa.
Comparisons on a linear and the Rozman logarithmic scale for dosage versus carcinogenicity in rodents are presented for methyl eugenol (ME), nitrosodiethylamine (NDEA), ethyl carbamate (EC) and 2-acetylaminofluorene (AAF). Each of these chemicals has been shown to be carcinogenic in experimental animals and, in addition, humans are regularly exposed to at least three of these compounds (ME, NDEA, EC) in foods. Although the source of adducts from AAF is not known, the aminofluorene (AF) adduct is present in humans. Plotted on the same graphs are either some doses from common foods (ME, NDEA, EC) or adducts (AF) on human haemoglobin, for perspective, with their thresholds for carcinogenesis in animals. Use of a linear scale when comparing doses administered to animals in studies of carcinogenicity with doses of those same chemicals to which humans are exposed does not provide useful, comparative information. On the other hand, the Rozman logarithmic scale for dose allows one to put these relative doses in perspective. It is also evident that forcing a linear extrapolation through the zero, zero origin does not agree with the experimental data. Further analyses for goodness of fit for these dose responses reveal that the dose response for three of these compounds (ME, NDEA, EC) appears to be linear with the logarithm of the dose. However, AAF appears to be linear with the logarithm of the dose for bladder, but not for liver. It is suggested that the high background incidence of tumours in the BALB/c StCrlfC3Hf/Nctr mouse liver may confound the interpretation of dose response from AAF carcinogenesis in mouse liver.
本文给出了甲基丁香酚(ME)、亚硝基二乙胺(NDEA)、氨基甲酸乙酯(EC)和2-乙酰氨基芴(AAF)在啮齿动物中剂量与致癌性的线性和罗兹曼对数尺度比较。这些化学物质均已在实验动物中显示出致癌性,此外,人类在食物中经常接触到其中至少三种化合物(ME、NDEA、EC)。虽然AAF加合物的来源尚不清楚,但氨基芴(AF)加合物存在于人类体内。为了便于比较,将常见食物中的一些剂量(ME、NDEA、EC)或人类血红蛋白上的加合物(AF)与它们在动物中的致癌阈值绘制在同一张图表上。在致癌性研究中,将给予动物的剂量与人类接触的相同化学物质的剂量进行比较时,使用线性尺度并不能提供有用的比较信息。另一方面,剂量的罗兹曼对数尺度使人们能够正确看待这些相对剂量。同样明显的是,通过零、零原点进行线性外推与实验数据不一致。对这些剂量反应的拟合优度进行的进一步分析表明,其中三种化合物(ME、NDEA、EC)的剂量反应似乎与剂量的对数呈线性关系。然而,AAF对膀胱的剂量反应似乎与剂量的对数呈线性关系,但对肝脏则不然。有人认为,BALB/c StCrlfC3Hf/Nctr小鼠肝脏中肿瘤的高背景发生率可能会混淆对AAF在小鼠肝脏中致癌作用剂量反应的解释。