Effect of captan on DNA synthesis in the liver and testes of rats

Rats were fed a diet containing 0.3% (w/w) captan for 2, 4 and 12 weeks and compared with controls, and with rats fed 0.02% (w/w) N-2-acetylaminofluorene (AAF). Cell loss was evaluated from the drop of previously [14C] labeled DNA and DNA synthesis was expressed as fractional incorporation of [3H] dThd into hepatic and testicular DNA. The feeding of AAF for 12 weeks produced in the liver a cell loss and a stimulation of DNA synthesis (+ 348%); in the testes, a cell loss but an inhibition of DNA synthesis (- 84%) occurred. The continuous feeding of captan produced no cytotoxic effect on the liver but increased hepatic DNA synthesis between 2 and 4 weeks of diet (+ 100%). Then, the synthesis induction seemed to reach a plateau until 12 weeks. The captan diet did not provoke any cytotoxic effect on testes until 4 weeks of feeding. At 12 weeks, some loss of testicular DNA and of [14C] labeling indicated a toxic effect of captan. The testicular DNA synthesis was clearly inhibited by captan diet at 4 weeks (- 22%), and the inhibition increased at 12 weeks (- 27%). Experiments done at a higher level of captan (1.5% in the diet) showed that the effect on DNA synthesis in liver and testes was dose-related.