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Effects of Strain and Age on Prophylaxis and Co-Carcinogenesis of Urethan-induced Mouse Lung Adenomas by Butylated Hydroxytoluene¹

Molecular and Environmental Toxicology Program, School of Pharmacy, University of Colorado, Boulder, Colorado 80309

A single i.p. injection of butylated hydroxytoluene (BHT) 6 h before a single urethan injection had varying effects on lung tumorigenesis in mice of different strains and ages. Strains exhibiting both high (A/J, SWR/J) and low (BALB/cByJ, 129/J, C57BL/6J) susceptibility to urethan tumorigenesis were tested in this study. BHT treatment decreased tumor multiplicity by an average of 32% in adult A/J mice but acted as a cocarcinogen by increasing tumor number 48% in adult SWR/J mice, 240% in adult C57BL/6J mice, 655% in adult 129/J mice, and 38% in 14-day-old A/J mice. The numbers of both alveolar type 2 cell-derived and bronchiolar Clara cell-derived lung adenomas were similarly affected by these BHT treatments. Such BHT pre-treatment had no effect on adenoma multiplicity in either young or adult BALB/cByJ mice. Multiplicity in young BALB/cByJ mice was also unaffected by chronic BHT administration following urethan, even though multiplicities increased several-fold with such treatment in adult mice of this strain. Since the mice showing co-carcinogenesis by BHT include strains which are both highly susceptible and relatively resistant to urethan induction of lung tumors, our results support a distinction between genes regulating susceptibility to urethan carcinogenesis and to tumor modulation by BHT.

¹ Supported by USPHS Grants ES02370 and CA33497 and Research Career Development Award CA00939 to A. M. M.

² To whom requests for reprints should be addressed.

Received 9/ 6/85. Revised 12/18/85. Accepted 1/ 3/86.