Cytotoxicity of aniline mustard glucuronide alone or in a combination with glucose in Walker cells in culture and sarcoma-180 tumour bearing animals.
The effect of aniline mustard glucuronide (AMG), p-hydroxyaniline mustard (HAM), and aniline mustard (AM), on Walker ascites tumour cells in vitro showed that AM in about 80 times more toxic than its glucuronide but HAM is at least 800 times more toxic. A non toxic dose of AMG became completely lethal to Walker tumour cells in vitro, if bovine liver beta-glucuronidase was added to the incubation medium. Prior treatment of Walker tumour cells in vitro with glucose, increased the breakdown of AMG to HAM within the intact cells, while a non-toxic dose of the glucuronide became completely lethal to cells pretreated with glucose. The administration of AMG in combination with glucose to animals bearing the highly resistant to alkylating agents Sarcoma-180 tumour, increased the toxicity of the glucuronide but produced a slight effect on tumour growth. Glucose administration in Sarcoma-180 and ADJ/PC6 tumour bearing animals did not alter the tumour intracellular pH determined in vivo indirectly from the distribution of the weak non-metabolizable organic acid 5,5-dimethyl-2,4-oxazolinedione (DMO) between intra- and extra-cellular water. The present data suggest that the combination of aniline mustard glucuronide with glucose, could be effective in those tumours which have a high beta-glucuronidase activity and a lower tumour intracellular pH could be induced by glucose.
D000816:Aniline Mustard / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents; D002279:Carcinoma 256, Walker / Q000188:drug therapy*; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D005947:Glucose / Q000494:pharmacology*; D009588:Nitrogen Mustard Compounds / Q000494:pharmacology*; D051381:Rats; D012510:Sarcoma 180 / Q000188:drug therapy*
D000970:Antineoplastic Agents; D009588:Nitrogen Mustard Compounds; C000929:hydroxyaniline mustard; C022211:4-(N,N-bis(2-chloroethyl)amino)phenyl O-beta-D-glucopyranosiduronic acid; D000816:Aniline Mustard; D005947:Glucose