THE ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS AGENT 3'-FLUOROTHYMIDINE INDUCES DNA-DAMAGE AND APOPTOSIS IN HUMAN LYMPHOBLASTOID-CELLS

Patients infected with the human immunodeficiency virus experienced se vere hematopoietic toxicity after treatment with the deoxynucleoside a nalog 3'-fluorothymidine (FLT), Using several methods for the analysis of genome integrity, including histochemical staining of the 3' ends of DNA and both conventional and pulsed-field agarose gel electrophore sis, we demonstrated that FLT caused extensive DNA fragmentation in CE M cells that was not observed when these cells were treated with other , less toxic thymidine analogs. In addition, a distinctive pattern of small DNA fragments that is characteristic of cells in the process of programmed cell death was observed in the genomic DNA of CEM cells tre ated with FLT. We conclude that FLT induces DNA fragmentation and apop tosis in a human cell line of hematopoietic origin, and we offer this observation as a possible explanation for the severe toxicity of FLT o bserved in vivo.