Genotoxicity assessment of HM10620 containing recombinant human interferon-alpha.
HM10620 is a recombinant human interferon-alpha (rhIFN-alpha) linked to immunoglobulin via N-terminal-specific non-peptidyl polyethylene glycol linker to improve the in vivo stability of interferon. Potential genotoxic effects of HM10620 in three short-term mutagenicity assays were investigated, which included the Ames assay, in vitro chromosomal aberration assay, and the in vivo micronucleus assay. HM10620 did not cause any mutation in the Ames assay tested using five tester strains at six concentrations of 6.25, 12.5, 25, 50, 100, and 200 microg/plate. To assess clastogenic effect, the in vitro chromosomal aberration assay and the in vivo micronucleus assay were performed using Chinese hamster lung cells and male ICR mice, respectively. Chromosomal aberration was not induced at the concentrations of 10, 20, and 40 microg/mL. Also, there was no difference in the incidence of micronucleated polychromatic erythrocytes at doses of 10, 20, and 40 mg/kg in male mice compared with the vehicle control group. Therefore, based on the results obtained from the three studies, it is concluded that HM10620 is not a mutagenic agent in bacterial cells and causes no chromosomal damage in mammalian cells both in vitro and in vivo.
Kim
Ji-Young
JY
Korea Institute of Toxicology, KRICT, Daejeon, Korea.
Lee
Young-Mi
YM
Koh
Woo Suk
WS
Kim
Choong-Yong
CY
Choi
In Young
IY
Kwon
Se Chang
SC
Lee
Gwan Sun
GS
Han
Jae Yong
JY
Lee
Michael
M
D000818:Animals; D016466:CHO Cells; D002869:Chromosome Aberrations / Q000139:chemically induced*; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects*; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry; D007370:Interferon Type I / Q000737:chemistry / Q000633:toxicity*; D016898:Interferon-alpha; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009152:Mutagenicity Tests; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D013047:Specific Pathogen-Free Organisms
D007136:Immunoglobulins; D007370:Interferon Type I; D016898:Interferon-alpha; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C519328:interferon-alpha, immunoglobulin-linked