Normal human lymphocytes were exposed to OH. radicals produced indirectly by exposure to H2O2 or directly by gamma irradiation. Using a flow cytometry technique to measure changes in nucleoid size, it was found that generation of OH. in each system produced a characteristic relaxation in nuclear supercoiling. Exposure of cells to H2O2 produced a metal-dependent step-wise relaxation in extracted nucleoids, while gamma irradiation induced a gradual dose-dependent increase in nucleoid size. The site-specific metal-dependent changes produced in lymphocytes incubated in H2O2 should also occur in gamma irradiation cells, but the characteristic effects on nuclear supercoiling would not be detected within the background of random DNA damage. The importance of metals in maintaining the supercoiled loop configuration of DNA within the protein matrix suggests that free radical damage at metal locations may be particularly toxic for the cell.
|Original language||English (US)|
|Number of pages||4|
|Journal||British Journal of Cancer|
|State||Published - 1988|
ASJC Scopus subject areas
- Cancer Research