Induction of micronuclei by low doses of azidothymidine (AZT)

The dideoxynucleoside azidothymidine (AZT; Zidovudine) was assessed for its ability to induce micronuclei in mouse erythrocytes at a low (therapeutic) dosage. Specifically, male and female BALB/c mice were treated via intraperitoneal injection 5 days a week for 2 weeks with saline or 17 mg AZT/kg body weight per day. Each animal was monitored for chemical-induced micronucleus formation over the course of the treatment regimen through the flow cytometric analysis of one-million pre-dosing and one million post-dosing peripheral blood erythrocytes. No significant change in micronucleus frequencies was observed for the vehicle control group as micronuclei continued to enter the peripheral blood pool at background levels. Conversely, the AZT-treated mice exhibited a statistically significant net increase in micronucleated cells over the course of dosing as erythrocytes with a high incidence of micronuclei entered the peripheral blood pool. The advantages of high throughout scoring protocols utilizing flow cytometry are discussed.