Enhancement of urethan tumorigenesis in mouse lung by butylated hydroxytoluene

Intraperitoneal injection of the antioxidant butylated hydroxytoluene (BHT) produces cell proliferation in mouse lungs within 2-4 days. We examined whether the presence of an increased number of proliferating lung cells would influence urethan tumorigenesis. Male Swiss-Webster mice were treated with 1 mg urethan/g before, during, or after BHT-stimulated cell growth in the lung. The number of pulmonary tumors found 13-15 weeks later was not different in BHT-treated mice compared to that in controls. On the other hand, repeated stimulation of cell growth after urethan treatment enhanced tumorigenesis. Male Swiss-Webster and A/J mice were given a single dose of urethan (1 mg/g) and, beginning 7 days later, weekly injections of BHT or corn oil. Repeated injections of BHT significantly increased the yield of lung tumors in both strains. Weekly injections of BHT into mice pretreated with 0.9% NaCl reduced the number of spontaneous pulmonary adenomas.