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.