AZT INCORPORATION INTO MITOCHONDRIA - STUDY IN A HUMAN MYELOID CELL-LINE

Zidovudine (AZT) is widely used in the treatment of human inmunodefici ency virus (HIV) infection because of its ability to act as a false su bstrate for the viral reverse transcriptase. AZT in the clinical setti ng has also been shown to produce significant hematologic and other to xicity, even though prior reports in the literature indicate that AZT is not readily incorporated into mammalian nuclear DNA, The human myel oid leukemia cell line HL-60 was grown in the presence of radiolabeled AZT or radiolabeled deoxythymidine as an in vitro model to study AZT toxicity for human myeloid cells, Radioactivity was reversibly incorpo rated into the mitochondria, suggesting that AZT toxicity may result i n part from its toxic effects on human mitochondria rather than on hum an nuclear DNA.