Intercalative DNA binding of model compounds derived from metabolites of 7,12-dimethylbenz[a]anthracene.
The DNA binding of nonreactive model compounds of metabolites of 7,12-dimethylbenz[a]-anthracene (DMBA)1 was studied in fluorescence quenching and fluorescence lifetime experiments. The model compounds examined were DMA and 8,9,10,11-tetrahydro-BA. DMA is a pi electron model of a highly carcinogenic bay region epoxide of DMBA, 8,9,10,11-tetrahydro-BA is a model compound of a less carcinogenic DMBA epoxide. The results indicate that the binding of DMA occurs primarily via intercalation. In 15% methanol the binding constant is 3.1 x 10(3) M-1. In 15% methanol and at DNA phosphate levels of 5.0 x 10(-4) M the intercalative binding of DMA is reduced by a factor of 6.2 when 5.0 x 10(-4) M Mg+2 is added. The DMA binding constant for intercalation is reduced by more than a factor of 4 when the methanol content of the solvent is increased from 0% to 20%. Finally DMA binding arising from pi interactions with the DNA bases is reduced more than 15 times when the DNA is denatured. For 8,9,10,11-tetrahydro-BA in 15% methanol the binding constant for intercalation is 6 times lower than that for DMA. These results along with previously reported binding data on other model compounds suggest that bay region metabolites of DMBA readily participate in physical pi stacking interactions with DNA.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000378:metabolism*; D000873:Anthracenes; D001551:Benz(a)Anthracenes; D001665:Binding Sites; D004247:DNA; D007364:Intercalating Agents; D008956:Models, Chemical; D012995:Solubility; D013050:Spectrometry, Fluorescence
D000873:Anthracenes; D001551:Benz(a)Anthracenes; D007364:Intercalating Agents; D015127:9,10-Dimethyl-1,2-benzanthracene; C063026:8,9,10,11-tetrahydrobenz(a)anthracene; D004247:DNA; C029126:9,10-dimethylanthracene