Inhibition of binding of 2-acetylaminofluorene to DNA by butylated hydroxytoluene and butylated hydroxyanisole in vitro.
Numerous studies have shown that the food antioxidants butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA), under specific exposure conditions, can inhibit hepatocarcinogenesis induced by various carcinogens. The purpose of the present work was to study the biochemical mechanisms responsible for the anticarcinogenic activity of BHA and BHT using in vitro systems. The effects of BHA and BHT on the binding of 2-acetylaminofluorene (2-AAF) to DNA was determined in a microsomal system and in primary cultures of rat hepatocytes. It was found that both antioxidants reduce the binding of 2-AAF and that of N-OH-2-acetylaminofluorene (N-OH-2-AAF) to calf thymus DNA in the presence of liver microsomes. The inhibition was however more pronounced with the parent compound. Lower levels of DNA binding were also detected in hepatocytes incubated with 2-AAF along with BHA or BHT. These results suggest that phenolic antioxidants can exert anticarcinogenic activity through modulation of carcinogen interaction with DNA which may reflect on alteration in carcinogen metabolic activation.
Richer
N
N
Department of Chemistry, Université du Québec à Montréal, Canada.
Marion
M
M
Denizeau
F
F
D015073:2-Acetylaminofluorene / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002083:Butylated Hydroxyanisole / Q000494:pharmacology*; D002084:Butylated Hydroxytoluene / Q000494:pharmacology*; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000975:Antioxidants; D002084:Butylated Hydroxytoluene; D002083:Butylated Hydroxyanisole; D004247:DNA; D015073:2-Acetylaminofluorene