[Nuclear DNA synthesis rate and labelling index: effects of carcinogenic and non-carcinogenic chemicals on its behaviour in the organism of growing CBA-mice. The thymidine-incorporation-screening-system (TSS) (author's transl)].
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.
D000818:Animals; D000831:Animals, Newborn; D001681:Biological Assay / Q000379:methods; D002273:Carcinogens / Q000032:analysis / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis*; D003864:Depression, Chemical; D005260:Female; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D013936:Thymidine / Q000378:metabolism
D002273:Carcinogens; D004247:DNA; D013936:Thymidine
Kern-DNS-Syntheserate und Markierungsindex in ihrem Verhalten bei Einwirkung carcinogener und nichtcarcinogener Substanzen auf den Organismus wachsender CBA-Mäuse. Das Thymidineinbau-Screening-System (TSS).