Effects of butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) on the acetylation of 2-aminofluorene and DNA-2-aminofluorene adducts in the rat

The effects of the synthetic phenolic antioxidants (butylated hydroxyanisole and butylated hydroxytoluene) on the in vivo acetylation of 2-aminofluorene and formation of DNA-2-aminofluorene adducts were investigated in male Sprague-Dawley rats. For in vitro examination, cytosols and intact cells, with or without butylated hydroxyanisole and butylated hydroxytoluene co-treatment, showed different percentages of 2-aminofluorene acetylation and DNA-2-aminofluorene adducts. For in vivo examination, pre-treatment of male rats with butylated hydroxyanisole and butylated hydroxytoluene (10 mg/kg) 48 h prior to the administration of 2-aminofluorene (50 mg/kg) resulted in 34% and 18%, 29% and 20% decreases, respectively, in the urinary and fecal recovery of N-acetyl-2-aminofluorene, and 34% and 19% decreases, respectively, in the metabolic clearance of 2-aminofluorene to N-acetyl-2-aminofluorene. Following exposure of rats to the 2-aminofluorene, with or without pretreatment with butylated hydroxyanisole and butylated hydroxytoluene, DNA-2-aminofluorene adducts were observed in the target tissues of liver and bladder, and also in circulating leukocytes. The DNA-2-aminofluorene adducts in liver, bladder, and leukocytes were decreased by pretreatment with butylated hydroxyanisole and butylated hydroxytoluene. This is the first demonstration that synthetic phenolic antioxidants decrease the N-acetylation of carcinogens and formation of DNA-carcinogen adducts in vivo.