ENHANCEMENT OF LUNG-TUMOR FORMATION IN MICE BY DIETARY BUTYLATED HYDROXYTOLUENE - DOSE TIME RELATIONSHIPS AND CELL-KINETICS

Abstract

Strain A/J mice given injections of 1000 mg urethan/kg and fed for 12 wk a diet containing 0.75% of [the antioxidant food additive] butylated hydroxytoluene (BHT) had significantly more tumors per lung 4 or 9 mo. later than animals given urethan and fed a control diet. A 2 wk exposure to dietary BHT (0.75%) was sufficient to significantly enhance tumor development, and the lowest effective BHT concentration was 0.1%, fed for 8 wk. Tumor development was also enhanced in animals treated once with 3-methylcholanthrene, benzo[a]pyrene, or N-nitrosodimethylamine and, beginning 24 h later, fed BHT for 8 wk. Cell kinetic studies showed that BHT given in the diet produced increased proliferation of type II alveolar cells during the first 2 wk and that initial cell proliferation was delayed in urethan-treated animals.