Different melphalan toxicity and DNA cross-linking in human melanoma cells as compared to phytohaemagglutinin-stimulated lymphocytes.
The cytotoxic effect of melphalan, measured as drug induced inhibition of cellular 3H-thymidine incorporation, was lower in RPMI 8322 melanoma cells than in phytohaemagglutinin-stimulated lymphocytes. Melphalan induced a 1.8-fold higher level of total cross-linking and a 1.5-fold higher level of DNA interstrand cross-linking in the phytohaemagglutinin-stimulated lymphocytes compared to the RPMI 8322 melanoma cells. In addition, higher levels of cross-linking were found in the newly synthesized DNA of lymphocytes in S-phase, as compared to S-phase RPMI 8322 cells. The cellular incorporation of 3H-melphalan was about four times higher in RPMI 8322 cells than in phytohaemagglutinin-stimulated lymphocytes. Thus, the lower toxicity of melphalan in RPMI 8322 cells and the lower levels of melphalan induced DNA cross-linking in these cells is due to intracellular factors rather than a lower cellular uptake of melphalan.
D002460:Cell Line; D003432:Cross-Linking Reagents; D004247:DNA / Q000378:metabolism*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism*; D008558:Melphalan / Q000378:metabolism / Q000494:pharmacology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism
D003432:Cross-Linking Reagents; D010835:Phytohemagglutinins; D004247:DNA; D008558:Melphalan; D013936:Thymidine