PREFERENTIAL INCORPORATION OF 3'-AZIDO-2',3'-DIDEOXYTHYMIDINE (AZT) IN TELOMERIC SEQUENCES OF CHO CELLS

摘要: 3'-Azido-2',3'-dideoxythymidine (AZT), the thymidine analogue used against human immunodeficiency virus 1 (HIV-1), exhibits bone marrow and blood toxicity in humans, presumably as result of genotoxic mechanisms induced by incorporation AZT into eukaryotic DNA. Preferential telomeric regions DNA Chinese hamster ovary (CHO) cells has been previously demonstrated immunofluorescence using anti-AZT antibodies. We quantitatively compared amount [H-3]-AZT bound to non-telomeric sequences CHO cell from exposed was digested a mixture restriction enzymes, frequent cutters overall genome, without sites repeat. As result, fraction (TF): isolated separation columns, comprised longer (> 2 kb) than (NTF). Radioactivity associated with each revealed three fold increase incorporated TF NTF. No preferential binding detected for [H-3]-thymidine (Tdr) or [H-3]-5'bromodeoxyuridine (BrdU) similar experiments AZT-treated mouse primary fibroblasts, large repeats that lack telomerase. When chromosomal ends high molecular weight [H-3]-AZT-DNA were Pal 31, radioactivity double Therefore immortalized but not fibroblasts (that telomerase) indirectly shows could be telomerase-mediated.