INDUCTION OF MICRONUCLEI BY LOW-DOSES OF AZIDOTHYMIDINE (AZT)

The dideoxynucleoside azidothymidine (AZT; Zidovudine) was assessed fo r its ability to induce micronuclei in mouse erythrocytes at a low (th erapeutic) dosage, Specifically, male and female BALB/c mice were trea ted via intraperitoneal injection 5 days a week for 2 weeks with salin e or 17 mg AZT/kg body weight per day. Each animal was monitored for c hemical-induced micronucleus formation over the course of the treatmen t regimen through the flow cytometric analysis of one million pre-dosi ng and one million post-dosing peripheral blood erythrocytes. No signi ficant 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 micronuc lei entered the peripheral blood pool. The advantages of high throughp ut scoring protocols utilizing flow cytometry are discussed.