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

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, CS7BL/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-dayold 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 ade noma multiplicity in either young or adult BALB/cByJ mice. Multiplicity in young BALB/cByJ mice was also unaffected by chronic BHT admin istration following urethan, even though multiplicities increased severalfold 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.