INHIBITION OF NO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE-INDUCED LYMPHOMA FORMATION BY OLTIPRAZ

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mutagenic and carcinogenic heterocyclic amine present in pyrolysate products of meat and fish and has been shown to induce tumors in the colon, mammar y gland, and possibly lymphatic system. Experiments were designed to e xamine the lymphoma-inducing capacity of PhIP and to test the inhibito ry effects of oltipraz on PhIP-induced lymphomas in male F344 rats. Be ginning at 5 weeks of age, groups of rats were fed the diets containin g 0, 200, and 400 ppm oltipraz with or without 100-400 ppm PhIP. All a nimals were continued on this regimen until the 58th week. The results indicate that administration of PhIP produced lymphomas in 75% of rat s. Most of the large lymphomas were thymomas (65%), and these lymphoma s developed in less than 6 months. Death of animals during the course of the study was due to suffocation produced by a large lymphoma that filled the entire thoracic cavity, resulting in collapse of the lungs. Administration of 200-400 ppm oltipraz significantly protected rats f rom PhIP-induced toxicity; most of the rats survived until termination of the experiments. It is noteworthy that the addition of oltipraz at 200 and 400 ppm in the diet suppressed the PhIP-induced lymphomas to 90-100%. In conclusion, PhIP-induced lymphomas in the laboratory rat a ppears to be a very useful model to analyze the genesis of lymphomas, and oltipraz serves as a potential chemopreventive agent for lymphomas .