Micronucleated Erythrocytes in Peripheral Blood of Newborn Rabbits after Exposure to Cyclophosphamide during Pregnancy

Abstract

There are ever increasing numbers of new chemicals and pharmaceutical products that have the potential  to induce birth defects or to cause damage during the perinatal period in humans. Many genotoxic compounds  possess teratogenic potential and induce the formation of micronuclei (MN). Objective: To demonstrate  that the New Zealand rabbit may be a useful animal model for the evaluation of transplacental genotoxicity  and potential teratogenicity of compounds by quantifying micronucleated erythrocytes (MNE) in  the peripheral blood of newborn rabbits following maternal exposure. Method: For each dose, a single  pregnant rabbit was injected daily on the 25th to 30th days of pregnancy with 1, 4, or 7 mg/kg cyclophosphamide  (CP) with one pregnant rabbit being treated with sterile water as the control. Following the daily  intramuscular administrations, a drop of blood was taken from six newborn rabbits from each female for  microscopic analyses. Results: When compared with controls, significant differences (p < 0.002) were  observed in the number of MNE and micronucleated polychromatic erythrocytes (MNPCE) from newborns  of females treated with 4 or 7 mg/kg CP, but not from newborns exposed to 1 mg/kg CP. No cytotoxic  effects were observed after the treatments. We concluded that the presence of MNE in newborn rabbits suggests  that the rabbit may be useful animal model for the detection and prevention of transplacental genotoxicity  and/or potential teratogenicity of compounds in the peripheral blood of newborn rabbits following  maternal exposure.