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Butylated Hydroxytoluene Exposure Is Necessary to Induce Lung Tumors in BALB Mice Treated with 3-Methylcholanthrene¹

Department of Pharmaceutical Sciences, School of Pharmacy, Colorado Cancer Center, University of Colorado Health Sciences Center, Denver, Colorado 80262 [A. M. M., K. M. K.], and Medical Research Council Toxicology Unit, University of Leicester, Leicester, United Kingdom [W. A. E., M. F. W. F.]

Chronic butylated hydroxytoluene (BHT) treatment after a single administration of a carcinogen increases lung tumor multiplicity in some inbred strains of mice. We report that BALB/cOla and BALB/cByJ mice given a low dose (10 µg/g of body weight) of 3-methylcholanthrene (MCA) develop no lung tumors unless this is followed by chronic BHT exposure. Slightly higher MCA doses (15 and 25 µg/g) induce low lung tumor multiplicities (0.6 and 1.9 tumors/mouse, respectively) that are increased 12–26-fold by chronic BHT administration. This low-dose MCA/BHT model in BALB mice will facilitate the identification of genes regulating susceptibility to lung tumor promotion and pulmonary chemopreventative agents that act at a postinitiation site.

¹ Supported by USPHS Grant CA33497 and by Grant 9510 from the American Institute for Cancer Research.

² To whom requests for reprints should be addressed, at Department of Pharmaceutical Sciences, School of Pharmacy. Colorado Cancer Center, University of Colorado Health Sciences Center, 4200 East 9th Street, Denver, CO 80262. Phone: (303) 315-4579; Fax: (303) 315-6281; E-mail: al.malkinson@uchsc.edu.

Received 4/ 7/97. Accepted 6/ 2/97.

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