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Inflammatory cell-mediated tumour progression and minisatellite mutation correlate with the decrease of antioxidative
F Okada1, K Nakai, T Kobayashi
1Laboratory of Pathology, Cancer Institute, Hokkaido University School of Medicine, Sapporo, Japan.
British Journal of Cancer
|February 23, 1999
Summary
Inflammation can accelerate tumor growth by increasing active oxygen species, especially when antioxidant enzyme levels like manganese superoxide dismutase (Mn-SOD) and glutathione peroxidase (GPchi) are low in tumor cells. This study investigated the link between inflammation, oxidative stress, and tumor progression in fibrosarcoma.
Area of Science:
- Oncology
- Biochemistry
- Immunology
Background:
- Fibrosarcoma clones (QR) exhibit weak tumorigenicity.
- Co-implantation with gelatin sponges enhances QR clone tumorigenicity via inflammation.
- Inflammation-induced active oxygen species may influence tumor progression.
Purpose of the Study:
- To investigate the role of intracellular antioxidative enzymes in inflammation-driven fibrosarcoma progression.
- To determine the correlation between antioxidant enzyme levels and tumor formation/mutation rates.
- To assess the impact of active oxygen species on DNA damage in fibrosarcoma.
Main Methods:
- Isolation and characterization of weakly tumorigenic fibrosarcoma (QR) clones.
- Co-implantation of QR clones with gelatin sponges in mice.
- Immunoblot analysis and enzyme activity assays for Mn-SOD and GPchi.
- Electron spin resonance (ESR) for superoxide-scavenging ability.
- DNA fingerprint analysis for minisatellite mutation (MSM) rates.
- Measurement of 8-hydroxydeoxyguanosine (8-OHdG) as a marker of DNA damage.
Main Results:
- Enhanced tumorigenicity of QR clones correlated inversely with Mn-SOD and GPchi levels.
- High Mn-SOD levels correlated with higher superoxide-scavenging ability.
- MSM rates were higher in subclones with low Mn-SOD and GPchi.
- Mannitol inhibited MSM in low-antioxidant subclones.
- Tumors from QR clones with high Mn-SOD/GPchi showed lower 8-OHdG levels, indicating reduced DNA damage.
Conclusions:
- Inflammation-induced active oxygen species accelerate tumor progression.
- Declined intracellular Mn-SOD and GPchi levels in tumor cells exacerbate this effect.
- Antioxidant enzymes play a crucial role in mitigating inflammation-associated tumor progression and DNA damage.