Selective in vivo inhibition of rat mammary 7,12-dimethylbenz[a]anthracene-DNA adduct formation by dietary butylated hydroxytoluene.
The in vivo formation of specific 7,12-dimethylbenz[a]-anthracene (DMBA)-DNA adducts in the mammary gland of the female Sprague-Dawley rat was studied in response to dietary butylated hydroxytoluene (BHT). Dietary BHT concentrations of 0.4 and 0.8% significantly inhibited total DMBA-DNA binding by 41.5 and 35.6% respectively, as compared to controls. However, the decrease in total binding associated with intake of BHT was not due to a uniform inhibition in the formation of all individual adducts. The formation of two adducts resulting from the binding of the anti-dihydrodiolepoxide of DMBA to deoxyguanosine (anti-dGuo) was significantly decreased by a combined average of 51.5% for rats fed BHT-supplemented diets as compared to controls. However, syn-derived DMBA-DNA adducts were not consistently inhibited by dietary BHT. Adduct formation resulting from the binding of the syn-dihydrodiolepoxide of DMBA to deoxyadenosine (syn-dAdo) was significantly inhibited only for rats fed a diet supplemented with 0.4% BHT. The formation of the syn-dGuo adduct was not affected by the feeding of BHT-supplemented diets. These results suggest that in vivo inhibition by BHT of mammary DNA adducts formed from the anti-diastereomer of DMBA may be an important contribution to the inhibitory effect of BHT on the initiation stage of DMBA-induced mammary carcinogenesis.
Division of Nutritional Sciences, University of Illinois, Urbana-Champaign 61801.
K W
KW
Singletary
J M
JM
Nelshoppen
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D002084:Butylated Hydroxytoluene / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism*; D018736:DNA Adducts; D003849:Deoxyguanosine / Q000378:metabolism; D005260:Female; D008321:Mammary Glands, Animal / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
C059444:7,12-dimethylbenz(a)anthracene-DNA adduct; D018736:DNA Adducts; D002084:Butylated Hydroxytoluene; D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA; D003849:Deoxyguanosine