Abstract
We have analyzed changes in the supercoiling of nucleoid DNA of murine fibroblasts cultured in the presence of hydralazine. The entire DNA attached to the nuclear matrix was extracted from the cells and sedimented in neutral sucrose density gradients containing ethidium bromide. Nucleoids from cells treated with hydralazine responded to increasing ethidium bromide concentrations in a different way than those from control cultures. That is, supercoiled loops of DNA unwound with lower concentrations of ethidium bromide sedimented less rapidly than those of control cells, indicating that hydralazine reduced the degree of DNA supercoiling. Also, nucleoids from the drug-treated cells resisted the transition from relaxed to positive supercoiling at higher concentrations of ethidium bromide. Changes in nucleoid DNA supercoiling correlated directly with the dose of hydralazine in the fibroblast culture.
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