Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Genotoxicity Study of HM10411, Recombinant Human Granulocyte Colony Stimulating Factor

재조합 인과립구 콜로니 자극인자 HM10411의 유전독성 연구

  • 권정 (한국화학연구원 부설 안전성평가연구소) ;
  • 이미가엘 (한국화학연구원 부설 안전성평가연구소) ;
  • 홍미영 (한국화학연구원 부설 안전성평가연구소) ;
  • 조지희 (한국화학연구원 부설 안전성평가연구소) ;
  • 정문구 (한국화학연구원 부설 안전성평가연구소) ;
  • 권세창 (한미 약품공업주식회사) ;
  • 이관순 (한미 약품공업주식회사)
  • Published : 2002.12.01
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Abstract

Mutagenic potential of HM10411 (recombinant human granulocyte colony stimulating factor) was evaluated by bacterial reverse mutation test, in vitro chromosome aberration test and in vivo micronucleus test. The bacterial reverse mutation test was performed using the histidine auxotroph strains of Salmonella typhimurium TA100, TA1535, TA98, TA1537 and tryptophan auxotroph strain of Escherichia coli WP2 uvrA. The negative results of the bacterial reverse mutation test suggest that HM10411 does not induce mutation, in the genome of Salmonella typhimurium and E. coli under the conditions used. In addition, it has little clastogenicity either in vitro chromosome aberration test or in vivo micronucleus test. For in vitro chromosomal aberration test, Chinese hamster lung(CHL) cells were exposed to HM10411 of 23, 46 or 92 $\mu\textrm{g}$/ml for 6 or 24 hours in the absence and for 6 hours in the presence of metabolic activation system. There was no significant increase in the number of aberrant metaphase in HM 10411-treated groups at any dose levels both in the presence and absence of metabolic activation system. The micronucleus test was carried out using specific pathogen free(SPF) 7-week old male ICR mice, The test item, HM10411 was intraperitoneally administered at 1150, 2300 or 4600 $\mu\textrm{g}$/kg once a day for 2 consecutive days. There was no significant increase in the frequencies of micronucleated polychromatic erythrocytes(PCEs) at any treated groups compared with negative control group. Therefore, these results demonstrate that the test item, HM10411, was not mutagenic under the condition of these studies.

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References

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