THE INCORPORATION OF RADIOLABELED SULFUR FROM CAPTAN INTO PROTEIN ANDITS IMPACT ON A DNA-BINDING STUDY

Repeated administration of high doses of captan is known to produce tu mours specifically in the duodenum of mice. Captan is not carcinogenic in the rat. In this study, DNA purified from the liver, stomach, duod enum and jejenum of mice dosed with S-35 radiolabelled captan was foun d to contain radioactivity equivalent to Covalent Binding Indices in t he range 38-91; that from the bone marrow had a CBI of 2.8. The distri bution of radioactivity between the various tissues did not reflect th e target organ specificity of captan. Attempts to further purify the D NA samples using caesium chloride gradients resulted in partial separa tion of the radioactivity from the DNA suggesting that covalent bindin g to the DNA may not have occurred. A study of the chemical breakdown of captan showed that captan is unstable, producing a variety of poten tially reactive species containing sulphur. Evidence was further obtai ned to show that the sulphur of captan is incorporated into endogenous amino acids and protein. Hepatic DNA from mice dosed with S-35 radiol abelled N-acetylcysteine, and two thiazolidine derivatives which are a nalogous to known metabolites of captan, was radiolabelled to a simila r extent to that from captan treated mice. Furthermore, the DNA from e ach of these treatments had similar properties on caesium chloride gra dients. It was concluded that the radioactivity associated with DNA in the captan DNA binding study was present in the low levels of protein which are always associated with purified DNA samples.