Graffi et al. (1-3) had proposed the use of exogenous
enzymes to toxify inactive transport forms of cancerostatic substances. For this purpose, the pH difference between normal tissues and the
tumor was to be exploited, which can be essentially increased by the application of
glucose and
inorganic phosphate (5-7). Earlier studies using
alpha-L-arabinofuranosidase obtained from Aspergillus niger have shown that the selectivity of
tumor chemotherapy can be increased in this way (4). The alpha-L-arabinofuranosidases known to date are stabile in a wide pH range (9). However, in some moulds we found pH-labile
enzymes of this kind that become irreversibly inactivated in the weakly alkaline or neutral pH range (10, 11). Studies on the distribution of the activity of a pH-labile
alpha-L-arabinofuranosidase from Glomerella myabana in
tumor-bearing mice have shown that this
enzyme is rapidly eliminated from the organism, in contrast to the pH-stable
alpha-L-arabinofuranosidase from A. niger. Apart from its excretion via kidney and liver, of importance is the inactivation of the
enzyme in the normal tissues. The additional application of
glucose strongly increased the activity of this
enzyme both in the
tumor and in normal tissues (12). By injecting alkaline solutions, stronger inactivation in normal tissues than in the
tumor was achieved (13). In the present paper, distribution of an
alpha-L-arabinofuranosidase from Fusarium species I 50 (11), inactive already at pH 7.0 (37 degrees C), was studied in
tumor-bearing mice. The activity of this
enzyme could be enriched under various conditions in the
tumor, and especially favorable proved to be the additional application of a combination of
glucose and
inorganic phosphate. Under these conditions, a higher activity than in the
tumor was demonstrable only in the kidney, which can possibly be eliminated in larger experimental animals by
diuretics or an appropriate alkaline administration. The investigations have shown that the pH-labile alpha-L-arabinofuranosidases, especially those of Fusarium sp., due to their pharmacokinetic behavior are better suited for use in our
therapy concept than the hitherto employed
enzyme from A. niger. More recently, Tietze (16) has proposed a similar
therapy concept, in which also the
glucose-increased pH difference between
tumor and normal tissue using
tumor-own
enzymes, exogenous
enzymes as well as transport forms of cancerostatic agents spontaneously hydrolysing under weakly acidic pH conditions is to be exploited.