Lethal activity and kinetic response of cultured human cells to 4'-(9-acridinylamino)methanesulfon-m-anisidine.
Cytotoxic and cytokinetic effects of 4'-(9-acridinylamino)methanesulfon-m-anisidine (m-AMSA) were studied on a cultured human colon carcinoma and on a human lymphoma (T1) cell line. Proliferating cells were more susceptible (10-fold) to the cytotoxic effect of m-AMSA than were nonproliferating cells. The agent had minimal effects on DNA synthesis. At comparable exposure doses on m-AMSA, the degree of lethal cell damage exceeded inhibition of DNA synthesis by 4-fold. Cells synchronized in different stages of the cell cycle were equally sensitive to the cytotoxic effects of the drug, although the major cytokinetic effect was a block in G2. A greater killing effect was obtained by fractionated delivery than by a comparable dose delivered at one. These results suggest that superior antitumor results may be achieved by adequately spaced low doses of m-AMSA in the treatment of sensitive human tumors.
D000609:Aminoacridines / Q000494:pharmacology*; D000677:Amsacrine; D000970:Antineoplastic Agents / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy; D004273:DNA, Neoplasm / Q000096:biosynthesis; D006801:Humans; D007364:Intercalating Agents / Q000494:pharmacology; D007700:Kinetics; D008223:Lymphoma / Q000188:drug therapy; D009374:Neoplasms, Experimental / Q000188:drug therapy*
D000609:Aminoacridines; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D007364:Intercalating Agents; D000677:Amsacrine