Transport of AMSA drugs into cells.
The uptake and efflux of radioactive 4'-(9-acridinylamino)methanesulphon-m-anisidide (mAMSA) and its inactive congener 4'-(9-acridinylamino)methanesulphon-o-anisidide (oAMSA) by PY815 mastocytoma cells were investigated. Both drugs were readily taken up by intact cells although only mAMSA caused DNA scission and is actively cytotoxic to PY815 cells. The microsomal enzyme inhibitors cimetidine or SKF525A increased drug uptake and decreased drug efflux suggesting that drug metabolism could explain the different activities of oAMSA and mAMSA.
D000609:Aminoacridines / Q000378:metabolism*; D000677:Amsacrine / Q000031:analogs & derivatives; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism*; D001692:Biological Transport; D002460:Cell Line; D004273:DNA, Neoplasm / Q000378:metabolism; D012515:Mast-Cell Sarcoma / Q000378:metabolism; D051379:Mice; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology
D000609:Aminoacridines; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D000677:Amsacrine; C033073:4'-(9-acridinylamino)methanesulfon-o-anisidide