Effects of cancer chemotherapeutic agents on testicular DNA synthesis in the rat. Evaluation of a short-term test for studies of the genetic toxicity of chemicals and drugs in vivo.
Changes in the rate of testicular DNA synthesis in the rat were studied at various times after single doses of 12 cancer chemotherapeutic agents. The animals were given intravenous injections of [14C]thymidine and [3H]thymidine 24 and 3 h, resp., before they were killed. By combining measurements of the free serum radioactivity and the testicular incorporation of the differentially labelled precursor, different response patterns were obtained for agents with different modes of action. The DNA-damaging agents cyclophosphamide, chlorambucil, thio-TEPA, busulphan, CCNU and procarbacine, after some delay, caused  a decrease of testicular thymidine incorporation and a corresponding increase of free serum radioactivity. The non-DNA-damaging agents 5-fluorouracil, methotrexate, hydroxyurea and cytosine arabinoside had a rapid effect on testicular thymidine incorporation and produced diverse response patterns different from that of the DNA-damaging agents. Actinomycin D and also vinblastine caused changes in testicular thymidine incorporation and showed response patterns different from those of the other agents. These results show that simple measurements of testicular DNA synthesis may provide useful information for the evaluation of genotoxic effects of chemical compounds and may help one to distinguish between DNA-damaging agents and metabolic inhibitors of DNA synthesis.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002066:Busulfan / Q000494:pharmacology; D002699:Chlorambucil / Q000494:pharmacology; D003520:Cyclophosphamide / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D008130:Lomustine / Q000494:pharmacology; D008297:Male; D009154:Mutation / Q000187:drug effects*; D011344:Procarbazine / Q000494:pharmacology; D051381:Rats; D013737:Testis / Q000187:drug effects / Q000378:metabolism*; D013852:Thiotepa / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism
D000970:Antineoplastic Agents; D002699:Chlorambucil; D011344:Procarbazine; D008130:Lomustine; D003520:Cyclophosphamide; D004247:DNA; D013852:Thiotepa; D002066:Busulfan; D013936:Thymidine