FAILURE OF DIETARY OLTIPRAZ TO INHIBIT BENZO[A]PYRENE-INDUCED LUNG TUMORIGENESIS IN STRAIN A MICE

Oltipraz (OLT), an antischistosomal agent, is known to inhibit tumorig enesis induced by a variety of carcinogens. In this study, we examined the ability of dietary oltipraz to inhibit benzo[a]pyrene (BP)-induce d pulmonary adenoma formation in A/J mice. In a 6-week study, the maxi mum tolerated dietary concentration of OLT was found to be 450 ppm. Ac cordingly, OLT was tested at 0.8 MTD and 0.4 MTD. OLT diets were initi ated 48 h prior to administration of a single i.p, dose of BP (100 mg/ kg). Control or experimental diets were continued for the duration of the study. At 6 months, mice treated with BP only had a multiplicity o f 9.0 tumors/animal and at 8.5 months, mice treated with BP only had a multiplicity of 21.4 tumors/animal. No inhibition of lung tumor forma tion by dietary OLT was observed at 6 or at 8.5 months after BP admini stration. In parallel experiments performed to assess the effects of O LT on pulmonary glutathione S-transferase activity, no induction of GS T activity was found at the various time points examined. Doses of OLT that induced GST activity and inhibited tumorigenesis in mice in expe riments conducted by other investigators would have exceeded the prede termined MTD for dietary OLT established in A/J mice in this study.