Senescence of nickel-transformed cells by an X chromosome: possible epigenetic control.
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.
Klein
C B
CB
Institute of Environmental Medicine, New York University Medical Center, NY 10016.
Conway
K
K
Wang
X W
XW
Bhamra
R K
RK
Lin
X H
XH
Cohen
M D
MD
Annab
L
L
Barrett
J C
JC
Costa
M
M
D000818:Animals; D002459:Cell Fusion; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000235:genetics*; D002872:Chromosome Deletion; D006224:Cricetinae; D003412:Cricetulus; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D051379:Mice; D009532:Nickel / Q000494:pharmacology*; D014960:X Chromosome / Q000187:drug effects*
D009532:Nickel; D007041:Hypoxanthine Phosphoribosyltransferase