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Chemopreventive Effects of myo-Inositol and Dexamethasone on Benzo[a]pyrene and 4-(Methylnitrosoamino)-1-(3-pyridyl)-1-butanone-induced Pulmonary Carcinogenesis in Female A/J Mice¹

Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota 55455

The objective of the present investigation was to prevent cancer of the lung by use of chemopreventive agents. Administrations of diets containing added myo-inositol or dexamethasone singly or in combination (the latter being the most potent) are being studied for this purpose. In previous work, the two compounds were shown to inhibit benzo(a)pyrene [B(a)P]-induced pulmonary adenoma formation in female A/J mice when fed during the postinitiation period [i.e., starting 1 week after the last of three administrations of B(a)P by oral intubation]. In the present investigation, a longer administration schedule was used, which encompasses both the initiation and the postinitiation stages of carcinogenesis. The feeding of the test compounds was started 2 weeks prior to the first dose of carcinogen and continued for the duration of the experiment. Under these conditions, reductions in tumor formation were: myo-inositol, 64%; dexamethasone, 56%; and both together, 86% (P < 0.001 for all three). Addition of both compounds resulted in the largest inhibition that has been achieved with this experimental model as used in these investigations. Studies have begun of inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced pulmonary adenoma formation by myo-inositol and dexamethasone. The two compounds inhibit pulmonary carcinogenesis when fed singly or in combination. When fed throughout the entire protocol, reductions in tumor formation were: myo-inositol, 46%; dexamethasone, 41%; and both together, 71% (P < 0.001 for all three). The results of these investigations demonstrate that myo-inositol and dexamethasone inhibit pulmonary adenoma formation resulting from exposures to two major pulmonary carcinogens, B(a)P and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.

¹ This work was supported by Grant RD-380 from the American Cancer Society and a grant from the Minnesota Soybean Research and Promotion Council.

² To whom requests for reprints should be addressed, at Department of Laboratory Medicine and Pathology, 6-133 Jackson Hall, University of Minnesota, Minneapolis, MN 55455.

Received 7/26/96. Accepted 10/ 2/96.

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