In vitro mode of action, pharmacokinetics, and organ specificity of poly (maleic acid-styrene)-conjugated neocarzinostatin, SMANCS.
The organ specificity and pharmacokinetics of SMANCS, poly (maleic acid-styrene)-conjugated neocarzinostatin (NCS), were investigated in rats. The drug activity accumulated primarily in the regional lymph nodes after subcutaneous injection. After intravenous injection, the drug was found in the kidney, lymph nodes, and bladder in very high concentrations, and in lesser concentrations in the bone marrow, lung, small intestine, liver and spleen. The urinary excretion rate and total recovery of the drug after intravenous injection were higher than those after subcutaneous injection. SMANCS, having a molecular weight of 2.5 x 10(4) daltons, was degraded in vivo to NCS (mol. wt. about 1.1 x 10(4)). This was also confirmed in vitro by incubating the drug with cell homogenates. SMANCS caused strand scission of DNA similarly to NCS in lymphoblastoid cells. However, in a cell-free system using colicin E1 plasmid DNA, a high concentration of SMANCS was required to produce DNA degradation detectable by the alkaline sucrose gradient method.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D007700:Kinetics; D008198:Lymph Nodes / Q000378:metabolism; D008207:Lymphatic Metastasis; D008297:Male; D008299:Maleic Anhydrides; D009928:Organ Specificity; D011137:Polystyrenes; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution; D009353:Zinostatin / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D008299:Maleic Anhydrides; D011137:Polystyrenes; C035755:poly(maleic acid-styrene)neocarzinostatin; D004247:DNA; D009353:Zinostatin