title: Senescence of nickel-transformed cells by an X chromosome: possible epigenetic control.
abstract: 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.
authors.affiliation: Institute of Environmental Medicine, New York University Medical Center, NY 10016.
authors.forename: C B
authors.initials: CB
authors.lastname: Klein
authors.forename: K
authors.initials: K
authors.lastname: Conway
authors.forename: X W
authors.initials: XW
authors.lastname: Wang
authors.forename: R K
authors.initials: RK
authors.lastname: Bhamra
authors.forename: X H
authors.initials: XH
authors.lastname: Lin
authors.forename: M D
authors.initials: MD
authors.lastname: Cohen
authors.forename: L
authors.initials: L
authors.lastname: Annab
authors.forename: J C
authors.initials: JC
authors.lastname: Barrett
authors.forename: M
authors.initials: M
authors.lastname: Costa
mesh_terms: 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*
chemical_list: D009532:Nickel; D007041:Hypoxanthine Phosphoribosyltransferase