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.
Chung
J G
JG
Department of Medicine, China Medical College, Taiwan, Republic of China. jgchung@mail.cmc.edu.tw
D000107:Acetylation / Q000187:drug effects; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001191:Arylamine N-Acetyltransferase / Q000097:blood / Q000378:metabolism; D002083:Butylated Hydroxyanisole / Q000494:pharmacology*; D002084:Butylated Hydroxytoluene / Q000494:pharmacology*; D002273:Carcinogens / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity; D018736:DNA Adducts / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005449:Fluorenes / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000201:enzymology
C052668:2-aminofluorene-DNA complex; D000975:Antioxidants; D002273:Carcinogens; D018736:DNA Adducts; D005449:Fluorenes; D002084:Butylated Hydroxytoluene; D002083:Butylated Hydroxyanisole; C012177:2-aminofluorene; D001191:Arylamine N-Acetyltransferase