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Genotoxicity studies on HM10760A, recombinant human erythropoietin conjugated to globin fragment

Cited 2 time in Web of Science Cited 2 time in Scopus
Authors
Kwon, Se Chang; Lee, Gwan Sun; Han, Jae Yong; Lee, Michael; Lee, Young-Mi; Koh, Woo Suk; Kim, Ji-Young
Issue Date
2010
Publisher
Taylor & Francis
Citation
Drug and Chemical Toxicology, vol.33 no.2, pp. 152-159
Keywords
ErythropoietinAmes assaychromosomal aberration assaymicronucleus assaygenotoxicity
Abstract
HM10760A is a recombinant human erythropoietin chemically conjugated to the N-terminus of human immunoglobulin Fc fragment through a polyethylene glycol linker. HM10760A was shown to have a relatively long half-life, compared with unconjugated recombinant erythropoietin. In this study, the genotoxicity of HM10760A was investigated by using a test battery of three different methods. In the Ames assay, five strains (TA100, TA1535, TA98, TA1537, and Escherichia coli WP2 uvrA) were tested at six concentrations of 3.13, 6.25, 12.5, 25, 50, and 100 μg/plate. HM10760A did not increase the number of revertant colonies in any tester strains with and without metabolic activation by rat-liver S9 mix. Subsequently, in vitro chromosomal aberration test, using Chinese hamster lung cells, were conducted at the concentrations of 25, 50, and 100 μg/mL. HM10760A did not induce chromosomal aberrations either in the short-period (6 hours) test with or without rat-liver S9 mix or in the continuous-treatment (24 hours) test. In the in vivo bone marrow micronucleus assay using the male ICR (imprinting control region) mouse, HM10760A was subcutaneously administered twice at 24-hour intervals at doses of 0, 150, 300, and 600 μg/kg. HM10760A produced a slight, but statistically significant, increase in the frequency of micronucleated polychromatic erythrocytes at 600 μg/kg. However, no biological significance was assumed, because this value was within the historical control range. From these findings obtained from the genotoxicity assays performed in this study, it appears unlikely that HM10760A acts as a genotoxic agent in vitro and in vivo.
ISSN
0148-0545
Language
English
URI
https://hdl.handle.net/10371/100284
DOI
https://doi.org/10.3109/01480540903196824
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College of Agriculture and Life Sciences (농업생명과학대학)Dept. of Food and Animal Biotechnology (식품·동물생명공학부)Journal Papers (저널논문_식품·동물생명공학부)
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