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Arsenic and old telomerase
© BioMed Central Ltd 2001
- Published: 27 November 2001
- Transcription Factor Activity
- Acute Promyelocytic Leukaemia
- Promyelocytic Leukaemia
- Relevant Dose
Although arsenic is effective in the treatment of acute promyelocytic leukaemia, it also has carcinogenic side effects, but the exact mode of action in carcinogenesis remains unclear. In the November Journal of Clinical Investigation, Wen-Chien Chou and colleagues from Johns Hopkins University School of Medicine, Baltimore, US show that, at clinically relevant doses, arsenic inhibits the transcription of the reverse-transcriptase subunit of the human telomerase gene (hTERT).
Chou et al. found that exposing NB4 leukemia cells to arsenic inhibited transcription of the hTERT gene by decreasing c-Myc and Sp1 transcription factor activities. Decreased hTERT activity led to chromosomal end lesions, which promoted either genomic instability and carcinogenesis or cancer cell death (J Clin Invest 2001, 108:1541-1547).
"These results may explain the seemingly paradoxical carcinogenic and antitumor effects of arsenic", concluded Chou.