TY - JOUR
T1 - Molecular genetic approaches to the study of cellular senescence
AU - Ning, Yi
AU - Pereira-Smith, Olivia M.
N1 - Funding Information:
We thank Susan Robetorye for excellent technical assistance. This work was supported by National Institutes of Health grants AG05333 and AG07123, a grant from the William Randolph
Funding Information:
Hearst Foundation and the Pilgeram Fund for Aging Research.
PY - 1991
Y1 - 1991
N2 - Normal cells in culture exhibit limited division potential, which is used as a model for cellular aging. In contrast, tumor-derived, carcinogen- or virus-transformed cells are capable of dividing indefinetely (immortal). Fusion of normal with immortal human cells yielded hybrids having limited life span, indicating that cellular senescence is a dominant phenotype and that immortality is recessive. Fusions of various immortal human cell lines with each other led to the identification of four complementation groups for indefinite division. In order to identify the chromosomes and genes involved in growth regulation, that had been modified in immortal cells, we used the technique of fusion to introduce either a normal human chromosome 11 or 4 into cell lines representative of the different complementation groups. Chromosome 11 had no effect on the in vitro life span of the different immortal human tumor lines. However, when a normal human chromosome 4 was introduced into cell lines assigned to complementation group B, the cells lost the immortal phenotype. No effect on the proliferation potential of cell lines representing of the other complementation groups was observed. These results suggest that a gene(s) on human chromosome 4 has been modified in immortal cell lines assigned to complementation group B, to allow escape from senescence. They also provide evidence for a genetic basis for cellular aging.
AB - Normal cells in culture exhibit limited division potential, which is used as a model for cellular aging. In contrast, tumor-derived, carcinogen- or virus-transformed cells are capable of dividing indefinetely (immortal). Fusion of normal with immortal human cells yielded hybrids having limited life span, indicating that cellular senescence is a dominant phenotype and that immortality is recessive. Fusions of various immortal human cell lines with each other led to the identification of four complementation groups for indefinite division. In order to identify the chromosomes and genes involved in growth regulation, that had been modified in immortal cells, we used the technique of fusion to introduce either a normal human chromosome 11 or 4 into cell lines representative of the different complementation groups. Chromosome 11 had no effect on the in vitro life span of the different immortal human tumor lines. However, when a normal human chromosome 4 was introduced into cell lines assigned to complementation group B, the cells lost the immortal phenotype. No effect on the proliferation potential of cell lines representing of the other complementation groups was observed. These results suggest that a gene(s) on human chromosome 4 has been modified in immortal cell lines assigned to complementation group B, to allow escape from senescence. They also provide evidence for a genetic basis for cellular aging.
KW - Cellular senescence
KW - Immortalization
KW - Microcell hybrids
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U2 - 10.1016/0921-8734(91)90021-3
DO - 10.1016/0921-8734(91)90021-3
M3 - Article
C2 - 1722020
AN - SCOPUS:0025720601
SN - 0921-8734
VL - 256
SP - 303
EP - 310
JO - Mutation Research DNAging
JF - Mutation Research DNAging
IS - 2-6
ER -