Effects of Low-Dose Gamma and Neutron Radiation on Genotoxicity and Cytotoxicity of Reticulocytes in a Mouse Model

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Nghi Phan
Nicole M. McFarlane
Jennifer Lemon
Doug R. Boreham

Abstract

Micronuclei are frequently enumerated in mouse peripheral blood to measure genotoxicity. Using a successful new automation of micronucleated reticulocyte (MN-RET) scoring, the effects of low-dose (< 1.0 Gy) gamma and neutron radiation on genotoxicity and cytotoxicity of reticulocytes in a mouse model were investigated. Forty-four (44 hrs) hours after whole-body irradiation, peripheral blood samples were collected for flow cytometric analysis. Flow cytometric measurements were restricted to the youngest fraction of reticulocytes based on trasferrin receptor (CD71) staining. Gamma and neutron irradiation induced significant (p<0.001) increases in the levels of &percnt;MN-RET the dose level increased. A definite positive dose response with respect to &percnt;MN-RET levels was observed in both gamma and neutron irradiated mice. At the 0.5, 0.75, 1.0 Gy levels, gamma radiation induced significantly (p<0.05) more &percnt;MN-RET than neutron radiation. In regards to &percnt;RET (a surrogate measure for cytotoxicity), gamma and neutron irradiation induced significant (p<0.001) decreases in the levels of &percnt;RET as the dose level increased. At the 0.25, 0.5, 1.0 Gy levels, gamma radiation induced significantly (p<0.05) more &percnt;RET than neutron radiation. As the dose increased in the gamma irradiated mice, the levels of &percnt;RET decreased, while the levels of &percnt;MN-RET increased (p<0.001). As the doses increased in the neutron irradiated mice, the levels of &percnt;RET decreased, while the levels of &percnt;MN-RET increased (p<0.001). The results suggest that neutron irradiation may be more cytotoxic (less &percnt;RET) than gamma irradiation; however, gamma irradiation may be producing cells with more chromosomal aberrations (more &percnt;MN-RET) than neutron irradiation.

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