DNA-BINDING STUDIES WITH ALLYLCHLORIDE AND ALLYLBROMIDE USING THE ISOLATED PERFUSED-RAT-LIVER TECHNIQUE

The isolated perfused liver technique has been adapted for DNA-binding studies of allyl compounds without the need for expensive radioactive labelled compounds or complex and protracted methods such as that including monoclonal antibodies. The technique was found to be easy to perform and gave reproducible results. The portioned administration of the test compounds (200-600 mg) was less damaging to the liver than the addition in a single dose. The liver functions could be held at nearly physiological values over a period of 10 hr. Three allylguanine adducts (O6-allylguanine, N2-allylguanine, 7-allylguanine) and two adenine adducts (N6-allyladenine and 3-allyladenine) could be detected in the hydrolysed DNA obtained from isolated perfused livers. These adducts demonstrate the modifications of DNA in mammalian liver and that a potential cancer-initiating effect must be considered with allyl compounds that possess alkylating activities. © 1990.