Treatment of mammalian cells with mimosine generates DNA breaks

Exponentially growing mouse erythroleukemia (MEL) cells and quiescent human peripheral blood lymphocytes (PBL) were treated with different concentrati ons of the nonprotein amino acid mimosine for 16 h. The treatment of the cy cling cell population with 400 mu M mimosine caused inhibition of DNA repli cation, changes in the progression of the cells in the cell cycle, and apop tosis. Nucleoid sedimentation analysis and comet assay were used to monitor the appearance and accumulation of DNA breaks. The rate of break accumulat ion was dose-dependent, did not depend on the stage of the cell cycle and w as not connected with the mechanism of DNA replication. The data indicate t hat the effects of mimosine on DNA synthesis and the cell cycle may be a re sult of introduction of breaks into DNA. (C) 2000 Elsevier Science B.V. All rights reserved.