Non-random distribution of dibenzo[a, e]fluoranthene-induced DNA adducts in DNA loops in mouse fibroblast nuclei

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Abstract
The three-dimensional distribution of nuclear DNA damage induced by dibenzo[a, e]fluoranthene (DBF), a potent carcinogen for mouse fibroblasts, has been examined. The intact supercoiled nuclear DNA obtained from nucleoids of mouse fibroblasts incubated with DBF was fractionated into loop DNA attached to the matrix (10%) and bulk loop DNA (90%). Preferential binding of DBF to the DNA of the extremities of loops, which are rich in regulatory sequences, was observed in all experiments. An increase of the preferential DBF binding was seen when fibroblasts were incubated with both DBF and novobiocin or hydroxyurea. The excess damage seen in loop DNA attached to the cage may be due to the functional state of chromatin proximate to the matrix and to the kinetics of diffusion to the interior of the nucleus of hydrophobic DBF metabolites accumulated in lipid-rich nuclear membrane.