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Stimulated human leukocytes cause activating mutations in the K-ras protooncogene
J H Jackson1, M Vollenweider, J Hill
1Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.
Oncogene
|June 12, 1997
Summary
Inflammatory leukocytes can cause DNA damage through hydroxyl radical (.OH) production, potentially activating the K-ras oncogene. This oncogene activation may be a key step in how leukocytes contribute to human cancer development.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Chronic inflammation involving leukocytes is linked to increased cancer risk.
- Leukocytes produce reactive oxygen species, including hydroxyl radical (.OH), which can damage DNA.
Purpose of the Study:
- To investigate the mechanism by which leukocyte-derived hydroxyl radical (.OH) contributes to carcinogenesis.
- To determine if .OH-induced DNA damage can activate the K-ras oncogene.
Main Methods:
- Stimulation of human leukocytes to induce .OH production.
- Assessment of DNA damage caused by leukocyte-derived .OH.
- Analysis of K-ras oncogene activation in response to .OH-induced DNA damage.
Main Results:
- Leukocyte-derived .OH was shown to cause DNA damage.
- This DNA damage was linked to the activation of the K-ras oncogene.
- A potential characteristic pattern of .OH-induced K-ras activation was observed.
Conclusions:
- Leukocyte-derived .OH-induced DNA damage can activate the K-ras oncogene.
- K-ras oncogene activation is a critical event in many human cancers.
- .OH-induced K-ras activation represents a plausible mechanism for leukocyte-driven carcinogenesis.