Differential DNA cross-linking and cytotoxicity in PHA-stimulated human lymphocytes exposed to melphalan, m-L-sarcolysin and peptichemio.
DNA interstrand, as well as DNA protein cross-linking, was more efficient in phytohaemagglutinin-stimulated human lymphocytes exposed to m-L-sarcolysin as compared to melphalan at equivalent concentrations of the drug. The cellular uptake of m-L-sarcolysin was more efficient as compared to melphalan. With peptichemio, a mixture of 6 peptides containing m-L-sarcolysin, an intermediate level of DNA cross-linking was found. The differences in DNA cross-linking between the 3 drugs were parallel to differences in cytotoxicity. Peptichemio has been ascribed anti-metabolic properties in addition to the alkylating properties conferred by its m-L-sarcolysin content. In the phytohaemagglutinin-stimulated lymphocytes, however, the effect of peptichemio seems linked to its capacity for DNA cross-linking.
D002470:Cell Survival / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects*; D006801:Humans; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008558:Melphalan / Q000031:analogs & derivatives* / Q000494:pharmacology*; D010440:Peptichemio / Q000494:pharmacology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D013237:Stereoisomerism
D003432:Cross-Linking Reagents; D010835:Phytohemagglutinins; C053596:metamelfalan; D004247:DNA; D010440:Peptichemio; D008558:Melphalan