Senescence of immortal human fibroblasts by the introduction of normal human chromosome 6
- Univ. of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, NJ (United States)
In these studies the authors show that introduction of a normal human chromosome 6 or 6q can suppress the immortal phenotype of simian virus 40-transformed human fibroblasts (SV/HF). Normal human fibroblasts have a limited life span in culture. Immortal clones of SV/HF displayed nonrandom rearrangements in chromosome 6. Single human chromosomes present in mouse/human monochromosomal hybrids were introduced into SV/HF via microcell fusion and maintained by selection for a dominant selectable marker gpt, previously integrated into the human chromosome. Clones of SV/HF cells bearing chromosome 6 displayed limited potential for cell division and morphological characteristics of senescent cells. The loss of chromosome 6 from the suppressed clones correlated with the reappearance of immortal clones. Introduced chromosome 6 in the senescing cells was distinguished from those of parental cells by analysis for DNA sequences specific for the donor chromosome. The results further show that suppression of immortal phenotype in SV/HF is specific to chromosome 6. Introduction of individual human chromosomes 2, 8, or 19 did not impart cellular senescence in SV/HF. In addition, introduction of chromosome 6 into human glioblastoma cells did not lead to senescence. Based upon these results the authors propose that at least one of the genes (SEN6) for cellular senescence in human fibroblasts is present on the long arm of chromosome 6.
- OSTI ID:
- 7029844
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 91:12; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
FIBROBLASTS
LIFE SPAN
HUMAN CHROMOSOME 6
DNA-CLONING
GENETIC MAPPING
ANIMAL CELLS
BIOTECHNOLOGY
CHROMOSOMES
CLONING
CONNECTIVE TISSUE CELLS
DNA HYBRIDIZATION
GENETIC ENGINEERING
HUMAN CHROMOSOMES
HYBRIDIZATION
MAPPING
NUCLEIC ACID HYBRIDIZATION
SOMATIC CELLS
550400* - Genetics