Chelating of iron and copper alters properties of DNA in L5178Y cells, as revealed by the comet assay

We have previously found different proportions of iron and copper in nuclei of two sublines of murine lymphoma L5178Y (LY) and proposed a model of chr omatin organization with these metal ions at the DNA attachment sites. We n ow examine the effect of chelators, desferal (DFO, iron-specific) and neocu preine (NEO, copper-specific) on DNA of LY-R and LY-S cells, using the come t and micronuclei frequency tests. There is less copper and more iron in LY -R nuclei than in LY-S nuclei. Accordingly, the effect of NEO is more marke d in LY-R than in LY-S cells and in both sublines it is expressed as enhanc ed tail moment (measure of DNA damage in the comet assay) and increased mic ronuclei frequency. On the contrary, the effect of DFO on the tail moment i s less pronounced in LY-R than in LY-S cells. With increasing DFO concentra tions, there is a gradual decrease in the tail moment values below the cont rol level in LY-S cells. In LY-R cells the tail moment values initially inc rease, then gradually decrease, eventually falling below the control level. This points to a dramatic conformational change that masks the effect of D NA discontinuities. The presence of the latter is indicated by the increase in micronuclei frequency. These results support the postulated differentia l role of iron and copper ions in maintaining the higher order DNA structur e in LY sublines, (C) 1999 Elsevier Science B.V. All rights reserved.