A conserved region in human and Chinese hamster X chromosomes can induce cellular senescence of nickel-transformed Chinese hamster cell lines.
Cellular senescence is the genetically programmed cessation of cellular proliferation. We have recently mapped a putative senescence gene(s) on the X chromosome of Chinese hamster embryo (CHE) cells. In the present study, we have utilized microcell-mediated chromosome transfer (microcell fusion) to test whether: (i) the human X chromosome exhibits similar genetic potential to induce senescence and (ii) the deletion or inactivation of the X-linked senescence gene(s) in CHE cells is associated with nickel-induced immortalization. A normal CHE or human X chromosome was first introduced into mouse-cell hybrids, then transferred by microcell fusion into a nickel-transformed, immortal male CHE cell line (Ni-2/TGR) with an X deletion (Xq1). Microcell fusion of the normal CHE X chromosome into tumorigenic Ni-2/TGR cells yielded senescence of all X recipient clones. The normal human X chromosome induced dominant senescence of tumorigenic Ni-2/TGR cells in only 17% of the resulting microcell hybrids (14/81). Karyotypic analyses of 13 non-senescing human X chromosome-derived microcell hybrid clones revealed that none of these clones retained the complete X. A normal CHE X chromosome induced senescence of 75% of hybrids obtained with another immortal and tumorigenic nickel-transformed male CHE cell line (Ni-6/TGR), which exhibited no visible deletion of the X chromosome, while the normal human X chromosome, only induced senescence in 19% of these hybrids. Transfer of the normal CHE or human X chromosome into spontaneously transformed and tumorigenic cell lines, CHO/TGR or V79/TGR, had little or no effect on their growth. These data suggest that both human and CHE cells possess similar X-linked genetic activities that regulate the process of cellular senescence, and that in Chinese hamster cells nickel-induced immortalization but not that of CHO or V79 cells is associated with inactivation of an X-linked senescence gene.
Wang
X W
XW
Institute of Environmental Medicine, New York University Medical Center, New York, NY 10016.
Lin
X
X
Klein
C B
CB
Bhamra
R K
RK
Lee
Y W
YW
Costa
M
M
D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D016922:Cellular Senescence; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D006822:Hybrid Cells; D007621:Karyotyping; D009532:Nickel / Q000633:toxicity*; D014960:X Chromosome
D009532:Nickel