Mitochondrial DNA mutations and 8-hydroxy-2'-deoxyguanosine Content in Japanese patients with urinary bladder and renal cancers
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Updated: Jul 18, 2026

HPLC Measurement of the DNA Oxidation Biomarker, 8-oxo-7,8-dihydro-2’-deoxyguanosine, in Cultured Cells and Animal Tissues
Published on: August 1, 2015
Takashi Wada1, Nozomu Tanji, Akira Ozawa
1Department of Urology, Ehime University School of Medicine, Tohon-city, Ehime, Japan.
Background:
Several recent studies have demonstrated the presence of mitochondrial DNA (mtDNA) mutations in various human cancers. The origin of these mutations may be attributable to oxidative damage from reactive oxygen species (ROS). In order to investigate the relationship between mtDNA mutations and ROS in human cancers, urinary bladder and renal cancers were examined for mutations in the displacement-loop (D-loop) region of mtDNA and for 8-hydroxy-2'-deoxyguanosine (8-OHdG) content.
Materials And Methods:
The D-loop region of mtDNA of Japanese patients with urinary bladder or renal cancers was examined by direct sequencing. The level of 8-OHdG was measured in the patients who had undergone radical cystectomy or nephrectomy from excised specimens.
Results:
Somatic mutations in the D-loop region were detected in 7 (23%) out of 31 patients with bladder cancer and 3 (14%) out of 21 patients with renal cancer. The most frequent mutations were in the poly(C) mononucleotide repeat located at positions 303 to 309. The levels of 8-OHdG in cancer tissues were significantly higher than in the neighboring non-cancerous tissues, but many of the cancers with an elevated 8-OHdG level did not display D-loop mutations.
Conclusion:
These results suggest that the D-loop region of mtDNA might have a genetic instability in cancer tissues independently from the 8-OHdG level.
Insights
Mitochondrial DNA (mtDNA) mutations were found in bladder and kidney cancers, but their presence was independent of oxidative damage markers like 8-hydroxy-2'-deoxyguanosine (8-OHdG). This suggests genetic instability in the mtDNA D-loop region of cancer tissues.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Mitochondrial DNA (mtDNA) mutations are increasingly found in human cancers.
- Oxidative damage from reactive oxygen species (ROS) is a potential cause of these mutations.
- Investigating the link between mtDNA mutations and ROS in cancer is crucial.
Purpose of the Study:
- To examine mutations in the mtDNA D-loop region in urinary bladder and renal cancers.
- To assess the levels of 8-hydroxy-2 -deoxyguanosine (8-OHdG) as a marker of oxidative damage in these cancers.
- To determine the relationship between mtDNA mutations and 8-OHdG levels in cancer tissues.
Main Methods:
- Direct sequencing of the mtDNA D-loop region in Japanese patients with bladder or renal cancer.
- Measurement of 8-OHdG levels in excised tumor specimens from patients who underwent surgery.
- Comparison of 8-OHdG levels in cancerous versus neighboring non-cancerous tissues.
Main Results:
- Somatic mutations in the mtDNA D-loop were detected in 23% of bladder cancer patients and 14% of renal cancer patients.
- The poly(C) repeat at positions 303-309 was the most common mutation site.
- While 8-OHdG levels were higher in cancer tissues, many tumors with elevated 8-OHdG did not show D-loop mutations.
Conclusions:
- The D-loop region of mtDNA exhibits genetic instability in cancer tissues.
- This genetic instability appears to be independent of the 8-OHdG level.
- Further research is needed to understand the mechanisms driving mtDNA D-loop mutations in cancer.
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