Biopolym. Cell. 2001; 17(6):551-555.
Investigation of DNA topoisomerase I as an autoantigen at the thyroid cancer
- Institute of Molecular Biology and Genetics, NAS of Ukraine
150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680
- R. E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine
45, Vasilkivska Str., Kyiv, Ukraine, 01022
- The University of York
Heslington, York, YO10 5DD, UK
- Pathomorphological Laboratory "BIONTEK"
52A/88, Komsomol'ska Str., Dnipropetrovs'k, Ukraine, 49000
The data concerning DNA-Topoisomerase I (Topo-I) from human placenta as an autoantigen at the thyroid cancer are presented. A new effective scheme of the Topo-I purification using the High-Trap columns is described, as well as the enzyme physico-chemical properties and its immunoreactivity in the ELJSA and immunoblotting. It was shown that 46 % of the sera from patients suffering the thyroid cancer were immunoreactive against Topo-I, 36 % of autoantibodies from thyroid cancer patients sera recognized sequential determinants on the Topo-I molecule. The highest levels of immunoreacivity were observed in the sera of thyroid cancer patients accompanied by autoimmune thyroiditis. We suggest a possible linkage between the autoimmune processes and malignization of the thyroid gland cells.
 Pommier Y, Pourquier P, Fan Y, Strumberg D. Mechanism of action of eukaryotic DNA topoisomerase I and drugs targeted to the enzyme. Biochim Biophys Acta. 1998;1400(1-3):83-105.
 Capranico G, Binaschi M. DNA sequence selectivity of topoisomerases and topoisomerase poisons. Biochim Biophys Acta. 1998;1400(1-3):185-94.
 Froelich-Ammon SJ, Osheroff N. Topoisomerase poisons: harnessing the dark side of enzyme mechanism. J Biol Chem. 1995;270(37):21429-32.
 Redinbo MR, Stewart L, Champoux JJ, Hol WG. Structural flexibility in human topoisomerase I revealed in multiple non-isomorphous crystal structures. J Mol Biol. 1999;292(3):685-96.
 Shero JH, Bordwell B, Rothfield NF, Earnshaw WC. High titers of autoantibodies to topoisomerase I (Scl-70) in sera from scleroderma patients. Science. 1986;231(4739):737-40.
 Guldner HH, Szostecki C, Vosberg HP, Lakomek HJ, Penner E, Bautz FA. Scl 70 autoantibodies from scleroderma patients recognize a 95 kDa protein identified as DNA topoisomerase I. Chromosoma. 1986;94(2):132-8.
 Johanet C, Agostini MM, Vayssairat M, Abuaf N. Anti-Scl-70 and anti-centromere autoantibodies. Biological markers of 2 forms of systemic scleroderma. Presse Med. 1989;18(5):207-11.
 Kato T, Yamamoto K, Takeuchi H, Okubo M, Hara E, Nakada S, Oda K, Ito K, Nishioka K. Identification of a universal B cell epitope on DNA topoisomerase I, an autoantigen associated with scleroderma. Arthritis Rheum. 1993;36(11):1580-7.
 Parmiani G. Tumor immunity as autoimmunity: tumor antigens include normal self proteins which stimulate anergic peripheral T cells. Immunol Today. 1993;14(11):536-8.
 Kyndt X, Hebbar M, Queyrel V, Hachulla E, Hatron PY, Devulder B. Systemic scleroderma and cancer. Search for predictive factors of cancer in 123 patients with scleroderma. Rev Med Interne. 1997;18(7):528-32.
 Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970;227(5259):680-5.
 Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248-54.
 Duguet M, Lavenot C, Harper F, Mirambeau G, De Recondo AM. DNA topoisomerases from rat liver: physiological variations. Nucleic Acids Res. 1983;11(4):1059-75.
 Castora FJ, Kelly WG. ATP inhibits nuclear and mitochondrial type I topoisomerases from human leukemia cells. Proc Natl Acad Sci U S A. 1986;83(6):1680-4.
 Matsiota P, Druet P, Dosquet P, Guilbert B, Avrameas S. Natural autoantibodies in systemic lupus erythematosus. Clin Exp Immunol. 1987;69(1):79-88.
 de Rooij DJ, van de Putte LB, Habets WJ, Verbeek AL, van Venrooij WJ. The use of immunoblotting to detect antibodies to nuclear and cytoplasmic antigens. Clinical and serological associations in rheumatic diseases. Scand J Rheumatol. 1988;17(5):353-64.
 Sidorik LL, Gudzera OI, Dragovoz VA, Tukalo MA, Beresten SF. Immuno-chemical non-cross-reactivity between eukaryotic and prokaryotic seryl-tRNA synthetases. FEBS Lett. 1991;292(1-2):76-8.
 Moll JW, Hooijkaas H, van Goorbergh BC, Roos LG, Henzen-Logmans SC, Vecht CJ. Systemic and anti-neuronal auto-antibodies in patients with paraneoplastic neurological disease. J Neurol. 1996;243(1):51-6.
 Kuwana M, Fujii T, Mimori T, Kaburaki J. Enhancement of anti-DNA topoisomerase I autoantibody response after lung cancer in patients with systemic sclerosis. A report of two cases. Arthritis Rheum. 1996;39(4):686-91.
 Papazov G, Baleva R, Chavrakov G, Mendizov I. Case of Hashimoto's toxicosis with occult thyroid carcinoma. Vutr Boles. 1981;20(5):105-11.