Reduction of 2-acetylaminofluorene-induced unscheduled DNA synthesis in human and rat hepatocytes by butylated hydroxytoluene.
Butylated hydroxytoluene (BHT) protected against DNA damage induced in rat hepatocytes by 2-acetylaminofluorene (2AAF) or N-hydroxy 2AAF as shown by a marked reduction of unscheduled DNA synthesis. BHT also inhibited 2AAF-induced DNA damage (as shown by reduced repair) in human hepatocytes. In addition, rats pre-treated with BHT in the diet (0.5% w/w for 10 days) provided hepatocytes which exhibited less unscheduled DNA synthesis than did hepatocytes from control rats when these cells were exposed to either 2AAF or N-hydroxy 2AAF. The results indicate both direct (in vitro) and indirect (by pre-treatment in vivo) inhibitory effects of BHT on the genotoxicity of 2AAF in liver cells, in accord with the reported anti-tumorigenicity in the liver. This effect contracts with a BHT-mediated increase in the efflux of 2AAF-derived mutagens from liver cells which may contribute to enhanced extrahepatic carcinogenesis.
Chipman
J K
JK
Department of Biochemistry, University of Birmingham, Great Britain.
Davies
J E
JE
D015073:2-Acetylaminofluorene / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D001711:Biotransformation; D002084:Butylated Hydroxytoluene / Q000008:administration & dosage / Q000494:pharmacology*; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D006801:Humans; D006881:Hydroxyacetylaminofluorene / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D002084:Butylated Hydroxytoluene; D006881:Hydroxyacetylaminofluorene; D015073:2-Acetylaminofluorene