Arsenic inhibition of telomerase transcription leads to genetic instability

Wen Chien Chou, Anita L. Hawkins, John F. Barrett, Constance A. Griffin, Chi V. Dang

Research output: Contribution to journalArticle

Abstract

Arsenic is effective in the treatment of acute promyelocytic leukemia. Paradoxically, it is also carcinogenic. In the process of elucidating a mechanism of arsenic resistance in a leukemia cell line, NB4, we discovered that arsenic exposure causes chromosomal abnormalities, with a preponderance of end-to-end fusions. These chromosomal end fusions suggested that telomerase activity may be inhibited by arsenic. We found that arsenic inhibits transcription of the hTERT gene, which encodes the reverse transcriptase subunit of human telomerase. This effect may in part be explained by decreased c-Myc and Sp1 transcription factor activities. Decreased telomerase activity leads to chromosomal end lesions, which promote either genomic instability and carcinogenesis or cancer cell death. These phenomena may explain the seemingly paradoxical carcinogenic and antitumor effects of arsenic.

Original languageEnglish (US)
Pages (from-to)1541-1547
Number of pages7
JournalJournal of Clinical Investigation
Volume108
Issue number10
DOIs
StatePublished - 2001

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Telomerase
Arsenic
Sp1 Transcription Factor
Acute Promyelocytic Leukemia
Genomic Instability
Chromosome Aberrations
Carcinogenesis
Leukemia
Cell Death
Cell Line
Genes
Neoplasms

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Chou, W. C., Hawkins, A. L., Barrett, J. F., Griffin, C. A., & Dang, C. V. (2001). Arsenic inhibition of telomerase transcription leads to genetic instability. Journal of Clinical Investigation, 108(10), 1541-1547. https://doi.org/10.1172/JCI200114064

Arsenic inhibition of telomerase transcription leads to genetic instability. / Chou, Wen Chien; Hawkins, Anita L.; Barrett, John F.; Griffin, Constance A.; Dang, Chi V.

In: Journal of Clinical Investigation, Vol. 108, No. 10, 2001, p. 1541-1547.

Research output: Contribution to journalArticle

Chou, WC, Hawkins, AL, Barrett, JF, Griffin, CA & Dang, CV 2001, 'Arsenic inhibition of telomerase transcription leads to genetic instability', Journal of Clinical Investigation, vol. 108, no. 10, pp. 1541-1547. https://doi.org/10.1172/JCI200114064
Chou, Wen Chien ; Hawkins, Anita L. ; Barrett, John F. ; Griffin, Constance A. ; Dang, Chi V. / Arsenic inhibition of telomerase transcription leads to genetic instability. In: Journal of Clinical Investigation. 2001 ; Vol. 108, No. 10. pp. 1541-1547.
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