Mutagenicity of recombinant antihemophilic factor (GC-gamma AHF).
This study was carried out to evaluate the mutagenic potential of recombinant antihemophilic factor VIII (GC-gamma AHF). Salmonella typhimurium (S. typhimurium) reversion assay with/without histidine moiety, chromosomal aberration assay on Chinese hamster lung (CHL) fibroblast cells and in vivo micronucleus assay using mouse bone marrow cells and supravital micronucleus assay using peripheral blood were performed. GC-gamma AHF containing histidine did show inconsistent and irregular mutagenic effects on S. typhimurium TA98, TA100, TA1535 and TA1537 both in the absence and presence of the metabolic activation system, however, GC-gamma AHF without histidine showed no mutagenic effects regardless of the metabolic activation system, thus suggesting that the histidine moiety in GC-gamma AHF might cause inconsistent mutagenic effect. Also GC-gamma AHF did not increase the number of cells having structural or numerical chromosome aberration in the cytogenetic test. In classical and supravital micronucleus assay, no significant increases were observed in the occurrence of micronucleated polychromatic erythrocytes and micronucleated peripheral lymphocytes in male ICR mice. These results strongly indicate that GC-gamma AHF has no genetic toxicity under these experimental conditions.
Shin
M
M
College of Veterinary Medicine, Seoul National University, Suwon, Korea.
Kim
B
B
Mar
W
W
Fang
M
M
Son
J
J
Kim
M
M
Kwak
H
H
Bae
M
M
Byun
T
T
Park
S
S
Chun
B
B
Byun
J
J
An
G
G
Lee
B
B
Cho
M
M
D000818:Animals; D002869:Chromosome Aberrations; D006224:Cricetinae; D003412:Cricetulus; D005169:Factor VIII / Q000008:administration & dosage / Q000633:toxicity*; D005347:Fibroblasts; D006801:Humans; D007274:Injections, Intraperitoneal; D008168:Lung / Q000166:cytology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000633:toxicity; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013347:Subcellular Fractions / Q000187:drug effects; D013778:Tetrazolium Salts; D013844:Thiazoles
D009153:Mutagens; D011994:Recombinant Proteins; D013778:Tetrazolium Salts; D013844:Thiazoles; D005169:Factor VIII; C022616:thiazolyl blue