Effect of hyaluronidase and PEG chain conjugation on the biologic and antitumor activity of RNase A.
Subcutaneous application of bovine RNase A conjugated to HYase (bovine hyaluronidase), polyethylene glycol (PEG) and HYase+PEG resulted in a marked reduction of the width of the spermatogenic layers of the mouse testes. The number of sperms in caput epididymidis was significantly decreased in mice injected with conjugated RNase A. There was not any significant embryotoxic effect of free RNase A even conjugated with HYse, PEG and HYse+PEG. The immunogenicity, expressed in production of antibodies against free RNase A or conjugates with PEG, was very low. However, the immunogenic action of this enzyme conjugated only to HYase was much higher and produced the same immunogenicity as HYase itself. The immunogenic effect of RNase A+HYase conjugate decreased when PEG was joined to this conjugate. The inhibitory effect of RNase A conjugated to HYase, PEG and HYase+PEG on human ML-2 cells studied in vitro, was practically ineffective. On the other side, when RNase A conjugated to HYase or PEG was administered intraperitoneally into the mice bearing human melanoma, the antitumor effect was pronounced.
Matousek
Josef
J
Institute of Animal Physiology and Genetics, Academy of Sciences of the Czech Republic, Libechov 277 21, Czech Republic. matousek@iapg.cas.cz
Poucková
Pavla
P
Hlousková
Daniela
D
Zadinová
Marie
M
Soucek
Josef
J
Skvor
Jirí
J
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D002417:Cattle; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D004357:Drug Synergism; D005260:Female; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D011092:Polyethylene Glycols / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D012259:Ribonuclease, Pancreatic / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D012756:Sheep; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
D000970:Antineoplastic Agents; D011092:Polyethylene Glycols; D012259:Ribonuclease, Pancreatic; D006821:Hyaluronoglucosaminidase