Failure of dietary oltipraz to inhibit benzo[a]pyrene-induced lung tumorigenesis in strain a mice.

Abstract

Oltipraz (OLT), an antischistosomal agent, is known to inhibit tumorigenesis induced by a variety of carcinogens. In this study, we examined the ability of dietary oltipraz to inhibit benzo[a]pyrene (BP)-induced pulmonary adenoma formation in A/J mice. In a 6-week study, the maximum tolerated dietary concentration of OLT was found to be 450 ppm. Accordingly, OLT was tested at 0.8 MTD and 0.4 MTD. OLT diets were initiated 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 of 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 formation by dietary OLT was observed at 6 or at 8.5 months after BP administration. In parallel experiments performed to assess the effects of OLT on pulmonary glutathione S-transferase activity, no induction of GST activity was found at the various time points examined. Doses of OLT that induced GST activity and inhibited tumorigenesis in mice in experiments conducted by other investigators would have exceeded the predetermined MTD for dietary OLT established in A/J mice in this study.