Efficacy of aerosolized oltipraz in the strain a mouse lung tumor model

2468 We have previously evaluated the chemopreventive efficacy of oltipraz, a glutathione-maintaining antioxidant and a dithiolthione against the strain A/J mouse lung adenoma induced by B[a] P (benzo[a]pyrene) when it was delivered directly to the respiratory tract as an aerosol. The study has shown that there is a significant decrease (p = 0.0004) in the number of tumors (gross lesions) at 105mg/m 3 of oltipraz exposed for 1.0 hr. In order to observe a dose response, the current study utilized two additional doses (10 and 30 mg/m 3 of air). Female Strain A/J mice were treated with oltipraz at three doses (10, 30 and 100 mg/m 3 ) using a Nose Only inhalation exposure system to deliver the aerosolized drug particulates directly to the respiratory tract for four weeks (5 days /week). During the second and third week, the animals received three doses of 2 mg B[a]P in 0.2 ml cotton seed oil. After the animals were shelved for another 16 weeks to develop tumors, they were sacrificed; lung tissues removed and fixed for tumor counting and pathological examination. The results indicated that, oltipraz did not show any toxicity in any of the exposure doses. There was very low spontaneous tumors in A/J mice with average 0.75 tumors per lung (cotton seed oil group), whereas, there was an average of 15.1 tumors per lung (20 fold induction) in B[a]P treated group. Gross evaluation of lung tumor post-exposure to otipraz exhibited significant reduction of tumor incidence and multiplicity. Oltipraz inhibited the tumor development in a dose-dependent manner with inhibition ranging from 37-50 %, when compared to the B[a]P only group. Analysis of the tumor multiplicity data showed that 67 % of the lungs were with 10 or more tumors in the B [a]P group, whereas, in oltipraz exposure group, there was a significant dose-dependent decrease in the number of lungs with 10 or more tumors (19-40 %). Pathological examination of lungs also revealed an oltipraz exposure related reduction in tumor incidence. The data from this study shows that oltipraz is an effective agent for lung cancer prevention, when delivered directly to the target tissue as aerosolized particulate (Supported by N01-CN-25112).