Comparative studies in induction of micronuclei by three genetically recombinant and urinary human erythropoietins

Comparative studies on the induction of micronucleated erythrocytes by three recombinant human erythropoietins (rhEPOs) such as epoetin alpha, epoetin beta, and SNB-5001, and by urinary human EPO (uhEPO) were carried out in vivo. Small but significant increases in the frequency of micronucleated polychromatic erythrocytes (MNPCEs) in bone marrow of mice following a single intraperitoneal (i.p.) administration of each of the three rhEPOs and uhEPO (25,000 IU/kg) were observed at the 48 h sampling time. Clear, significant increases in the frequency of micronucleated reticulocytes (MNRETs) in the peripheral blood of mice similarly treated with the four hEPOs at 50,000 IU/kg were noted at the 48, 72 and 96 h sampling times. When mice were dosed with 50,000 IU/kg of each of the hEPOs once each day for 6 days and micronucleus preparations were made 24 h after the last administration, micronucleus induction in the bone marrow was not clearly demonstrated. As before, MNRETs in these mice were significantly induced in all cases. Consequently, it was concluded that induction of MNPCEs and MNRETs was a common characteristic of both native and genetically recombinant EPO.