Senescence of Nickel-Transformed Cells by an X Chromosome: Possible Epigenetic Control

• Published in: Science (American Association for the Advancement of Science) Vol. 251; no. 4995; pp. 796 - 799
• Main Authors: Klein, Catherine B., Conway, Kathleen, Wang, Xin Wei, Bharma, Rupinder K., Lin, Xinhua, Cohen, Mitchell D., Annab, Lois, Barrett, J. Carl, Costa, Max
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 15-02-1991; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: 560300 - Chemicals Metabolism & Toxicology; Aging; ANIMAL CELLS; ANIMALS; Biological and medical sciences; Cancer; CARCINOGENESIS; Cell aging; Cell Fusion; Cell Line, Transformed; Cell lines; Cell physiology; Cell regulation; Cell Survival - genetics; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cell Transformation, Neoplastic - chemically induced; Cell Transformation, Neoplastic - genetics; CELL TRANSFORMATIONS; Cells; Cellular biology; Cellular control mechanisms; Cellular senescence; CHEMICAL REACTIONS; Chromosome Deletion; CHROMOSOMES; Cricetinae; Cricetulus; Deoxyribonucleic acid; DNA; ELEMENTS; Epigenesis; Fundamental and applied biological sciences. Psychology; GENE REGULATION; GENES; Genetics; HAMSTERS; HETEROCHROMOSOMES; Hybridity; Hypoxanthine Phosphoribosyltransferase - genetics; MAMMALS; Medical research; METABOLISM; METALS; METHYLATION; Mice; Molecular and cellular biology; NICKEL; Nickel - pharmacology; NUCLEIC ACIDS; ONCOGENIC TRANSFORMATIONS; ORGANIC COMPOUNDS; PATHOGENESIS; RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT; RODENTS; Somatic cells; Transformed cell line; TRANSITION ELEMENTS; Tumor cell line; Tumors; VERTEBRATES; X CHROMOSOME; X Chromosome - drug effects; Senescence; Ageing; Rodentia; Cell transformation; Genetic transfer; Vertebrata; Mammalia; Cell line; Cell death; DNA; Epigenetics; X-Chromosome; Methylation; Hamster
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1990442

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.