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PMID: 3200838 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Hypoxia induces DNA overreplication and enhances metastatic potential of murine tumor cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 85 ·No. 24 ·1988-12-00 ·Pages 9533-7

Young SD, Marshall RS, Hill RP

Abstract

Cultured cells subjected to oxygen deprivation have been shown to undergo anomalous DNA synthesis, which can result in DNA overreplication and the generation of cellular variants [Rice, G. C., Hoy, C. & Schimke, R. T. (1986) Proc. Natl. Acad. Sci. USA 83, 5978-5982]. In the present study, murine tumor cells were exposed to severe hypoxia and then tested for their ability to form experimental metastases. Upon reoxygenation, cells transiently, yet dramatically, increased their metastatic potential. Flow cytometric analysis confirmed that hypoxia and reoxygenation induced cell cycle perturbations and DNA overreplication in these tumor cell lines. Fibrosarcoma cells with overreplicated DNA isolated by fluorescence-activated cell sorting proved to be highly metastatic, although cells with 2-4 times the haploid DNA content in populations treated with hypoxia were also markedly more metastatic than oxic populations. These results support the hypothesis that hypoxic conditions existing in regions of solid tumors promote cellular heterogeneity and tumor progression.

MeSH Terms
Animals Cell Line Cell Transformation, Neoplastic DNA Replication Fibrosarcoma/genetics Flow Cytometry Gene Amplification Melanoma/genetics Mice Neoplasm Metastasis Oxygen
Chemicals
Oxygen
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Young S D
Ontario Cancer Institute, Physics Division, Toronto, Canada.
Marshall R S
Hill R P
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.85.24.9533
Published
1988-12-00
Pages
9533-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC282788
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.85.24.9533 PMC Full Text View journal details
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