Metabolism and mechanism of the antileukemic action of isomeric aryldimethyltriazenes.
Mice bearing TLX5 lymphoma or P388 leukemia were treated with ortho, meta, and para isomers of the salts of (3,3-dimethyl-1-triazeno)benzoic acid. Survival time was markedly increased in mice given the para isomer; effects were less pronounced for the meta isomer and absent for the ortho isomer. The in vivo effects of the tested compounds did not correlate either with the propensity of the drugs to undergo oxidative N-demethylation and hydrolysis to diazonium cations or with in vitro cytotoxicity for TLX5 lymphoma cells. The para isomer did not reduce the number and viability of peritoneal TLX5 lymphoma cells after in vivo and in vitro treatment, whereas a dose-dependent reduction that can even result in the absence of clonogenic tumor cells occurred in the brains of the treated animals. These data indicate that the increased survival time of the tumor-bearing mice treated with the para isomer should not be ascribed to cytotoxic effects of the drug and might be attributed to inhibition of tumor cell dissemination in various organs of the host, as already observed for solid metastasizing tumors in mice.
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism*; D001711:Biotransformation; D001932:Brain Neoplasms / Q000378:metabolism / Q000556:secondary; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D007536:Isomerism; D007700:Kinetics; D007942:Leukemia, Experimental / Q000188:drug therapy / Q000378:metabolism*; D008223:Lymphoma / Q000378:metabolism / Q000556:secondary; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D013329:Structure-Activity Relationship; D014226:Triazenes / Q000378:metabolism* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D014226:Triazenes; C030838:1-(4-carboxyphenyl)-3,3-dimethyltriazene