EFFECT OF METHYLGLYOXAL ON HUMAN LEUKEMIA-60 CELL-GROWTH - MODIFICATION OF DNA, G(1) GROWTH ARREST AND INDUCTION OF APOPTOSIS

Methylglyoxal induced growth arrest in the G(1) phase of the cell cycl e and toxicity in human leukaemia 60 cells in vitro. Inhibition of DNA synthesis but not inhibition of RNA synthesis, protein synthesis or i nhibition of glyceraldehyde-3-phosphate dehydrogenase activity correla ted with cytotoxicity. Incubation of human leukaemia 60 cells with met hylglyoxal led to the rapid accumulation of adducts of methylglyoxal w ith DNA, and a lower accumulation of methylglyoxal adducts with RNA an d protein in the initial hour of culture; fragmentation of nuclear DNA characteristic of apoptosis developed in the second hour of culture. Methylglyoxal induced apoptosis in human leukaemia 60 cells but did no t affect the growth and viability of concanavalin A-stimulated human p eripheral lymphocytes in vitro, These effects confirm and further subs tantiate the anti-proliferative anti-tumour activity of methylglyoxal in vitro, which may mediate the anti-tumour activity of glyoxalase I i nhibitors in vivo. Copyright (C) 1996 Elsevier Science Ltd.