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Science 15 February 1991:
Vol. 251. no. 4995, pp. 796 - 799
DOI: 10.1126/science.1990442
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Articles

Science, Vol 251, Issue 4995, 796-799
Copyright © 1991 by American Association for the Advancement of Science

articles

Senescence of nickel-transformed cells by an X chromosome: possible epigenetic control

CB Klein, K Conway, XW Wang, RK Bhamra, XH Lin, MD Cohen, L Annab, JC Barrett, and M Costa

Institute of Environmental Medicine, New York University Medical Center, NY 10016.

Transfer of a normal Chinese hamster X chromosome (carried in a mouse A9 donor cell line) to a nickel-transformed Chinese hamster cell line with an Xq chromosome deletion resulted in senescense of these previously immortal cells. At early passages of the A9/CX donor cells, the hamster X chromosome was highly active, inducing senescence in 100% of the colonies obtained after its transfer into the nickel-transformed cells. However, senescence was reduced to 50% when Chinese hamster X chromosomes were transferred from later passage A9 cells. Full senescing activity of the intact hamster X chromosome was restored by treatment of the donor mouse cells with 5-azacytidine, which induced demethylation of DNA. These results suggest that a senescence gene or genes, which may be located on the Chinese hamster X chromosome, can be regulated by DNA methylation, and that escape from senescence and possibly loss of tumor suppressor gene activity can occur by epigenetic mechanisms.


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