Does bleeding induce micronuclei via erythropoietin in Han-Wistar rats?

Abstract

The effects of both intravenous administration of recombinant human erythropoietin (rhEPO) and blood withdrawal, either individually or in combination, on the frequency of micronucleated immature erythrocytes (MIE) in the bone marrow were investigated in 10-week old male Han Wistar rats. Clear increases in MIE frequency and evidence of erythroid hyperplasia were seen in the bone marrow after 1350 IU kg⁻¹ rhEPO but only marginal increases in MIE were seen at the lower dose of 135 IU kg⁻¹. At the lower dose, blood levels of rhEPO were found to be approximately 120 pg mL⁻¹ within one hour of dosing. Withdrawal of 5 blood samples of 0.45 mL on each occasion during 24 hours, the maximum allowed by the Home Office licence, did not increase MIE frequency but did result in levels of endogenous EPO of 15–19 pg mL⁻¹ 24 to 72 hours after the start of treatment, with some evidence of increased erythropoiesis. Although the increased plasma amounts of EPO, resulting from blood withdrawal, were lower than the blood levels achieved by the administration of exogenous rhEPO that were required to give increases in micronucleus frequency, the possibility that blood withdrawal might influence the MIE response to genotoxins cannot be totally excluded without further investigation.