Mutagenesis induced by the tumor microenvironment

Jianling Yuan, Peter M. Glazer

Research output: Contribution to journalArticlepeer-review

103 Scopus citations


Genomic instability is a commonly observed feature of tumors. Most investigations addressing the mechanism of tumor progression have focused on the genetic factors that may play a role. Growing evidence now suggests that, in addition to these endogenous factors, the exogenous environment within solid tumors may by itself be mutagenic and constitute a significant source of genetic instability. The tumor microenvironment is characterized by regions of fluctuating hypoxia, low pH, and nutrient deprivation. Each of these microenvironmental factors has been shown to cause severe disturbance in cell metabolism and physiology. Both in vivo and in vitro data demonstrate that exposure of tumor cells to adverse conditions can directly cause mutations, contributing to genetic instability. In this review, we will reexamine the current body of evidence on the role of the tumor microenvironment in inducing mutagenesis and consequent tumor progression.

Original languageEnglish (US)
Pages (from-to)439-446
Number of pages8
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Issue number1-2
StatePublished - May 25 1998
Externally publishedYes

Bibliographical note

Funding Information:
We thank S. Rockwell, L. Guo, S. Peretz, P. Chan, L. Cabral, L. Narayanan, R. Franklin, and S.J. Baserga for their help. This work was supported by the American Cancer Society (VM189). J. Yuan is supported by an MD/PhD fellowship from the Yale University School of Medicine.


  • Genetic instability
  • Hypoxia
  • pH
  • supF


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