Melphalan-induced DNA cross-linking in human melanoma cells and phytohaemagglutinin-stimulated lymphocytes in relation to intracellular drug content and cellular levels of glutathione.
Melphalan-induced DNA cross-linking was compared in a human melanoma cell line (RPMI 8322) and in phytohaemagglutinin (PHA)-stimulated lymphocytes. In both cell types a delayed induction of DNA cross-links was observed, with maximum DNA cross-linking occurring 6-12 hours after drug exposure. Significantly higher peak levels of DNA cross-links were found in PHA-stimulated lymphocytes, total DNA cross-linking being 2.5 times and DNA interstrand cross-linking 2.2 times higher. The intracellular content of free melphalan was 1.3-fold higher in RPMI 8322 cells, thus the lower DNA cross-linking was not due to a lower drug concentration in these cells. RPMI 8322 cells had a 1.8-fold higher level of glutathione, possibly indicating a higher capacity of these cells to inactivate melphalan.
D002460:Cell Line; D002478:Cells, Cultured; D003432:Cross-Linking Reagents; D004273:DNA, Neoplasm / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism*; D008558:Melphalan / Q000378:metabolism / Q000494:pharmacology*; D010835:Phytohemagglutinins / Q000494:pharmacology
D003432:Cross-Linking Reagents; D004273:DNA, Neoplasm; D010835:Phytohemagglutinins; D005978:Glutathione; D008558:Melphalan