Unlike the bovine pancreatic ribonuclease (RNAase A), bovine seminal ribonuclease (BS RNAase) displays various biological activities including antitumor cytotoxicity. To learn more about its antitumor activity, we investigated BS RNAase effect on athymic nude mice bearing various tumors. BS RNAase (250 micrograms per mouse per day) was administered to the mice with prostate carcinoma for three weeks by three different routes (intraperitoneally--i.p., subcutaneously--s.c., and intratumorally-i.t.). Administration i.p. was ineffective, while s.c. administration reduced significantly size of tumors and i.t. administration abolished half of the tumors in treated mice. The i.t. administration of BS RNase to nude mice bearing melanoma showed even better results. Eighty % of mice were without tumors and in the other mice the tumors were significantly diminished. The best antitumor effect was obtained in case of seminoma. All mice bearing this tumor were cured after ten doses of BS RNAase.

• MeSH
• antitumorózní látky aplikace a dávkování   terapeutické užití   MeSH
• endoribonukleasy aplikace a dávkování   terapeutické užití   MeSH
• experimentální nádory farmakoterapie   MeSH
• léky antitumorózní - screeningové testy MeSH
• melanom farmakoterapie   MeSH
• myši nahé MeSH
• myši MeSH
• nádory prostaty farmakoterapie   MeSH
• seminom farmakoterapie   MeSH
• skot MeSH
• transplantace heterologní MeSH
• transplantace nádorů MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• skot MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antitumorózní látky MeSH
• endoribonukleasy MeSH
• ribonuclease SPL MeSH Prohlížeč

Bovine seminal ribonuclease (BS-RNase) is a dimer in which the subunits are cross-linked by disulfide bonds between Cys31 of one subunit and Cys32 of the other. Dimeric BS-RNase is resistant to ribonuclease inhibitor (RI), a protein endogenous to mammalian cells, and is toxic to a variety of cell types. Monomeric BS-RNase (like its homolog, RNase A) is bound tightly by RI and is not cytotoxic. The three-dimensional structure of the RI·RNase A complex suggests that carboxymethylation of C32S BS-RNase (to give MCM31) or C31S BS-RNase (MCM32) could diminish affinity for RI. We find that MCM31 and MCM32 are not only resistant to RI, but are also aspermatogenic to mice. In contrast to the aspermatogenic activity of dimeric BS-RNase, that of MCM31 and MCM32 is directed only at spermatogenic layers. Intratesticular injection of MCM31 or MCM32 affects neither the diameter of seminiferous tubules nor the weight of testes. Also in contrast to wild-type BS-RNase, MCM31 and MCM32 are not toxic to other cell types. Direct immunofluorescence reveals that MCM31 and MCM32 bind only to spermatogonia and primary spermatocytes. This cell specificity makes MCM31 and MCM32 of potential use in seminoma therapy and contraception.

• Publikační typ
• časopisecké články MeSH

BACKGROUND: Bovine seminal ribonuclease (BS RNase) was determined to have a specific suppressive effect on the proliferation of T lymphocytes in vitro. Its immunosuppressive effect was proven in skin grafting in mice as well. METHODS: The immunosuppressive effect of BS RNase was evaluated in tissue cultures and on a model of corneal transplantation in rabbits. The penetration of BS RNase into the anterior chamber was detected by immunoblotting of anterior chamber fluid obtained from animals treated either topically or subconjunctivally. RESULTS: In vitro blastic transformation of mouse T lymphocytes was significantly inhibited by BS RNase (concentrations 15-250 micrograms/ml). No such effect was observed on B lymphocytes. In the rabbit model of corneal graft rejection, BS RNase injected subconjunctivally prolonged mean graft survival time significantly (33.4 days) compared with placebo (salt solution; MST 17.7 days). No BS RNase was detected by immunoblotting in anterior chamber fluid after either topical or subconjunctival application. CONCLUSION: BS RNase showed significant immunosuppressive effect both in the blastic transformation test and in the rabbit high-risk model of corneal transplantation. Negative results of anterior chamber fluid immunoblotting indicate poor absorption of the drug.

• MeSH
• aktivace lymfocytů účinky léků   MeSH
• aplikace lokální MeSH
• buněčné dělení MeSH
• endoribonukleasy farmakokinetika   farmakologie   MeSH
• imunoblotting MeSH
• imunosupresivní léčba metody   MeSH
• injekce MeSH
• konjunktiva MeSH
• králíci MeSH
• kultivované buňky MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• přední komora oční metabolismus   MeSH
• přežívání štěpu účinky léků   MeSH
• rejekce štěpu imunologie   metabolismus   prevence a kontrola   MeSH
• skot MeSH
• T-lymfocyty účinky léků   imunologie   MeSH
• transplantace rohovky * imunologie   patologie   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• mužské pohlaví MeSH
• myši MeSH
• skot MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• endoribonukleasy MeSH
• ribonuclease SPL MeSH Prohlížeč