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Published on: August 12, 2011
Non-heme dioxygenases in tumor hypoxia: They're all bound with the same fate
1Department of Biotechnology, Indian Institute of Technology Hyderabad, Kandi 502285, Hyderabad, Telangana, India.
Abstract:
Tumor tissues are known to harbor hypoxic areas. The hypoxic microenvironment promotes angiogenesis. Hypoxic tumor cells also manifest genome instability. DNA damage repair pathways, such as double-strand break repair, mismatch repair and base excision repair are known to be altered during hypoxia. This review is focused on the non-heme Fe(II) and 2-oxoglutarate-dependent dioxygenases which are involved in repair of DNA alkylation adducts. Activities of these DNA repair enzymes are completely oxygen-dependent and little information is available about inhibition of these enzymes during hypoxia. While impairment of function of non-heme dioxygenase during tumor hypoxia has been implicated in different studies, the possible outcomes with respect to mutagenesis and genomic instability are explored here.
Insights
Hypoxia in tumors impairs oxygen-dependent DNA repair enzymes, specifically non-heme Fe(II) and 2-oxoglutarate-dependent dioxygenases. This impairment may drive mutagenesis and genomic instability in cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Tumor tissues frequently contain hypoxic regions.
- Hypoxia promotes angiogenesis and genomic instability in cancer cells.
- DNA damage repair pathways are altered under hypoxic conditions.
Purpose of the Study:
- To review the role of non-heme Fe(II) and 2-oxoglutarate-dependent dioxygenases in DNA alkylation adduct repair.
- To explore the impact of hypoxia on these oxygen-dependent DNA repair enzymes.
- To investigate the link between impaired dioxygenase function, mutagenesis, and genomic instability in tumors.
Main Methods:
- Literature review focusing on DNA repair mechanisms.
- Analysis of studies implicating non-heme dioxygenase function in tumor hypoxia.
- Exploration of potential outcomes regarding mutagenesis and genomic instability.
Main Results:
- Non-heme Fe(II) and 2-oxoglutarate-dependent dioxygenases are crucial for repairing DNA alkylation adducts.
- The activity of these enzymes is strictly oxygen-dependent.
- Limited information exists on the inhibition of these enzymes during tumor hypoxia.
Conclusions:
- Impairment of non-heme dioxygenase function during tumor hypoxia is implicated in cancer progression.
- This impairment may contribute significantly to mutagenesis and genomic instability.
- Further research is needed to understand the full consequences of dioxygenase inhibition in hypoxic tumors.
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