Amlacher E, Rudolph C
Exp Pathol (Jena). 1978;16(1-6):69-82.
During the last few decades there has been an extraordinary accumulation of man-made chemicals in the human environment. There is a growing consensus in oncology that a large proportion of human cancers are environmental in origin by exposure of man to such carcinogenic chemicals. These chemicals in the majority of all cases have not been tested to prove their carcinogenicity. Testing of new chemical compounds is needful prior to their introduction into commerce, foods, agriculture or the working places to prevent human cancer. To test such a large number of possibly carcinogenic chemicals, economical and rapidly practicable bioassays are necessary. In the following we compare some well known bioassays with our autoradiographic thymidine-incorporation-screening-system and other assays based on biochemical quantification of DNA synthesis as parameter for identification of carcinogenic substances. The partial inhibition of the whole DNA synthesis in a proliferating cell population after treatment with toxic and carcinogenic chemicals is an early common response especially in hepatectomized animal, livers caused by the effects of those substances. However, by quantitative evaluation of the nuclear DNA synthesis rate as a basic parameter using autoradiographs of kidney and liver of juvenile growing CBA-mice, it is possible to differentiate carcinogenic from non-carcinogenic chemicals by means of silver grain counting after 3H-TdR incorporation. Contrarily the "whole DNA synthesis" expressed by the percentual 3H-labelling index of kidney and liver did not permit such a differentiation in our experimental arrangement. We could demonstrate that carcinogenic compounds of different chemical classes partially inhibit the nuclear DNA synthesis rate significantly over a time period longer than 24 hours. The tested non-carcinogenic compounds did not show this suppressive effect on the nuclear DNA synthesis rate.
在过去几十年间，人造化学物质在人类环境中大量累积。肿瘤学界越来越达成共识，即大部分人类癌症源于人类接触此类致癌化学物质的环境因素。在大多数情况下，这些化学物质并未经过测试以证明其致癌性。在新的化合物投入商业、食品、农业或工作场所之前进行测试，以预防人类癌症是很有必要的。为了测试如此大量可能致癌的化学物质，经济且快速可行的生物测定法是必需的。在接下来的内容中，我们将一些知名的生物测定法与我们的放射自显影胸腺嘧啶核苷掺入筛选系统以及其他基于DNA合成生化定量作为致癌物鉴定参数的测定法进行比较。用有毒和致癌化学物质处理后，增殖细胞群体中整个DNA合成的部分抑制是一种早期常见反应，尤其是在肝切除动物的肝脏中，这是由这些物质的作用引起的。然而，通过使用幼年生长的CBA小鼠肾脏和肝脏的放射自显影片，将核DNA合成速率作为基本参数进行定量评估，在掺入3H - TdR后通过银颗粒计数可以区分致癌化学物质和非致癌化学物质。相反，在我们的实验设置中，用肾脏和肝脏的3H标记指数百分比表示的“整个DNA合成”不允许进行这种区分。我们可以证明，不同化学类别的致癌化合物在超过24小时的时间段内会部分显著抑制核DNA合成速率。测试的非致癌化合物对核DNA合成速率没有显示出这种抑制作用。
