Clearance of phenylalanine ammonia-lyase from normal and tumor-bearing mice.
Yeast phenylalanine ammonia-lyase was administered i.p. to normal and tumor-bearing mice, and its clearance from plasma was studied. Single and multiple weekly injections at dosages of 10,20,50 and 100 units/kg were administered to C57BL female, C57BL X DBA/2F1 male, and A/J female mice. L5178Y murine lymphoblastic leukemia, B16 melanoma, BW10232 adenocarcinoma, and 15091A anaplastic carcinoma were implanted 7 to 11 days prior to enzyme injection in the appropriate host. After a single injection, the average plasma half-lives of phenylalanine ammonia-lyase were 18 to 24 hr in all groups studied. While the other tumors had no effect on the plasma level of phenylalanine ammonia-lyase after a single injection, L5178Y murine lymphoblastic leukemia and 15091A anaplastic carcinoma significantly depressed the maximal level of phenylalanine ammonia-lyase attained in the plasma. After repeated injections of phenylalanine ammonia-lyase, the initial plasma enzyme level was significantly reduced when 20 units/kg were administered, and the clearance of the enzyme from the plasma was greatly accelerated regardless of the amount administered. Furthermore, in tumor-bearing mice, the rate of clearance was significantly more rapid than in the appropriate non-tumor-bearing control.
D000230:Adenocarcinoma / Q000097:blood; D000642:Ammonia-Lyases / Q000097:blood*; D000818:Animals; D000917:Antibody Formation; D000941:Antigens; D002277:Carcinoma / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D007274:Injections, Intraperitoneal; D007945:Leukemia, Lymphoid / Q000097:blood; D008297:Male; D008545:Melanoma / Q000097:blood; D008657:Metabolic Clearance Rate; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009374:Neoplasms, Experimental / Q000097:blood* / Q000276:immunology; D010650:Phenylalanine Ammonia-Lyase / Q000008:administration & dosage / Q000097:blood* / Q000276:immunology
D000941:Antigens; D000642:Ammonia-Lyases; D010650:Phenylalanine Ammonia-Lyase