Mutagenicity of recombinant antihemophilic factor (GC-gamma AHF)

This study was carried out to evaluate the mutagenic potential of recombina nt antihemophilic factor VIII (GC-gamma AHF). Salmonella typhimurium (S. ty phimurium) reversion assay with/without histidine moiety, chromosomal aberr ation assay on Chinese hamster lung (CHL) fibroblast cells and in vivo micr onucleus assay using mouse bone marrow cells and supravital micronucleus as say using peripheral blood were performed. GC-gamma AHF containing histidin e did show inconsistent and irregular mutagenic effects on S. typhimurium T A98, TA100, TA1535 and TA1537 both in the absence and presence of the metab olic activation system, however, GG-gamma AHF without histidine showed no m utagenic effects regardless of the metabolic activation system, thus sugges ting that the histidine moiety in GC-gamma AHF might cause inconsistent mut agenic effect. Also GC-gamma AHF did not increase the number of cells havin g 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 an d micronucleated peripheral lymphocytes in male ICR mice. These results str ongly indicate that GC-gamma AHF has no generic toxicity under these experi mental conditions.