Comprehensive comparison of the cytotoxic activities of onconase and bovine seminal ribonuclease

被引:38
作者
Matousek, J
Soucek, J
Slavík, T
Tománek, M
Lee, JE
Raines, RT [1 ]
机构
[1] Univ Wisconsin, Dept Biochem, 433 Babcock Dr, Madison, WI 53706 USA
[2] Acad Sci Czech Republ, Inst Anim Physiol & Genet, Libechov 27721, Czech Republic
[3] Inst Hematol & Blood Transfus, Prague 2 12820, Czech Republic
[4] Inst Anim Prod, Prague 10 10000, Czech Republic
[5] Univ Wisconsin, Dept Chem, Madison, WI 53706 USA
来源
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY | 2003年 / 136卷 / 04期
关键词
aspermatogenesis; cancer; chemotherapy; embryotoxicity epididymides; immunogenicity; leydig cells; Ribonuclease A; ribonuclease inhibitor; testes;
D O I
10.1016/j.cca.2003.10.005
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Onconase (ONC) and bovine seminal ribonuclease (BS-RNase) are homologs of bovine pancreatic ribonuclease (RNase A). Unlike RNase A, ONC and BS-RNase can evade the cytosolic ribonuclease inhibitor protein and are potent cytotoxins. Here, the endogenous cytotoxic activities of ONC and BS-RNase are compared in a wide variety of assays. Injections of ONC into one or both testes of mice and rats evokes a stronger aspermatogenic activity than does the injection of BS-RNase. Epididymides exposed to ONC lose mass and all sperm. Testicular tissue is gradually colonized by immunite and fibrocytic cells. Yet, Leydig cells are always present and functional in the ligamented parts of testicles injected with ONC or BS-RNase. ONC is likewise more toxic to mouse embryos than is BS-RNase, both in vitro and in vivo. The antiproliferative effect of ONC on human tumor cell line ML-2 and lymphocytes in a mixed lymphocyte culture is also more pronounced than is that of BS-RNase. The number of granulocyte-macrophage colony-forming units is repressed almost completely by ONC, whereas a five-fold higher dose of BS-RNase does not cause substantial inhibition. In mice, ONC is less immunogenic than BS-RNase but more immunogenic than RNase A. Together, these data indicate that ONC is a pluripotent cytotoxin, and serves as the benchmark with which to gauge the cytotoxicity of other ribonucleases. (C) 2003 Elsevier Inc. All rights reserved.
引用
收藏
页码:343 / 356
页数:14
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