Selective tumor DNA synthesis inhibition: in vivo prodrug activation by an exogenous enzyme.
Using the combination of alpha-L-arabinofuranosidase from Aspergillus niger with beta-peltatin A-alpha-L-arabinofuranoside, the selective effect of a new cancer of chemotherapy method based on a pH-dependent activation of cancerostatic prodrugs by exogenous enzymes was studied. In comparative experiments the selectivity of prodrug activation was measured by 3H-thymidine incorporation in tumor and normal tissues of CBA mice inoculated im with the transplantable mammary carcinoma, MA-21224. The results show that this special type of carrier principle may lead to a higher degree of selectivity than the usual direct application of cancerostatic drugs.
D000818:Animals; D001089:Arabinose / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000494:pharmacology; D004261:DNA Replication / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D006026:Glycoside Hydrolases / Q000494:pharmacology* / Q000627:therapeutic use; D006863:Hydrogen-Ion Concentration; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism*; D051379:Mice; D008808:Mice, Inbred CBA; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D004273:DNA, Neoplasm; C016032:beta-peltatin A-alpha-L-arabinofuranoside; D003520:Cyclophosphamide; D001089:Arabinose; D006026:Glycoside Hydrolases; D011034:Podophyllotoxin