[Pharmacokinetic studies of the activity of a pH-labile alpha-L-arabinofuranosidase following i.v. injection into tumor-bearing mice].
In order to increase the selectivity of tumor chemotherapy, Graffi et al. have proposed the application of xenogenic enzymes, which are able to split transport forms of carcinostatics under the pH-conditions in the tumor more vigorously than in the normal tissues. This paper describes the distribution within the body and elimination of the activity of the pH-labile alpha-L-arabinofuranosidase from G. myabena compared with the pH-stable enzyme from A. niger, using tumor bearing mice. In vitro, the pH labile arabinosidase was irreversibly inactivated within a few minutes at pH 7.4 and 37 degrees C; however at pH 6.5 it remained active even after several hours. After injection, this enzyme activity was eliminated from the organism by excretion and inactivation within a few hours. Hereby a relatively favourable distribution of the enzyme activity for therapeutic application was reached after 60 minutes. At this time higher activity than in the tumor was measured only in the kidney. The application of glucose led to a strong increase of the enzyme activity in both tumor and normal tissues. This effect was also seen in tumor free mice. In further experiments it will be tried to find out conditions which reduce the glucose induced acidosis. The activity and distribution of the pH-stabile enzyme from A. niger were not influenced by glucose application.
Butschak
G
G
Zentralinstitut für Molekularbiologie der Akademie der Wissenschaften der DDR, Berlin-Buch.
Schulze
B
B
Küster
A
A
Niederhausen
T
T
Niemeyer
U
U
Graffi
A
A
D000818:Animals; D001203:Ascomycota / Q000201:enzymology*; D001234:Aspergillus niger / Q000201:enzymology*; D005947:Glucose / Q000494:pharmacology; D006026:Glycoside Hydrolases / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D012513:Sarcoma, Experimental / Q000378:metabolism*; D013268:Stimulation, Chemical; D014018:Tissue Distribution
D006026:Glycoside Hydrolases; C019713:alpha-N-arabinofuranosidase; D005947:Glucose
Pharmakokinetische Untersuchungen der Aktivität einer pH-labilen alpha-L-Arabinofuranosidase nach i.v.-Injektion in tumortragende Mäuse.