The in vivo uptake of tritiated thymidine as a potential short-term test of toxic effects of polycyclic aromatic hydrocarbons in different organs

Abstract

A rapid in vivo test for toxicity is described where the test substance is allowed to distribute and metabolize in the intact mouse. Quantitative data are provided on the effect of 3 different polycyclic aromatic hydrocarbons on the DNA turnover in various organs, measured as the incorporation of tritiated thymidine. In accordance with previously reported carcinogenic potencies, 7,12-dimethylbenz[α]anthracene (DMBA) was more potent in inhibiting the thymidine incorporation than benzo[α]pyrene (B[α]P). The inhibitory effect was most pronounced in spleen, lung, pancreas, small intestine and kidney, resulting in a decrease in incorporated activity with up to 80%. There was no evidence for the existence of specific target organs for DMBAs effects on thymidine incorporation as indicated by an inhibitory action in all organs studies. A decreased thymidine incorporation after administration of DMBA could also be demonstrated with whole-body autoradiography. The inhibitory effect of B[α]P was most pronounced in thymus, spleen, small intestine and testis, the average decrease of incorporated activity being more than 40% after 48 h. Contrary to the wide action of the above mentioned polycyclic aromatic hydrocarbons, an equimolar dose of anthracene lacked significant effects on the various organs.