Mitochondrial DNA mutations and 8-hydroxy-2'-deoxyguanosine Content in Japanese patients with urinary bladder and renal cancers.
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.


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.


CONCLUSIONS
These results suggest that the D-loop region of mtDNA might have a genetic instability in cancer tissues independently from the 8-OHdG level.
Wada
Takashi
T
Department of Urology, Ehime University School of Medicine, Tohon-city, Ehime, Japan.
Tanji
Nozomu
N
Ozawa
Akira
A
Wang
Jianbo
J
Shimamoto
Kenji
K
Sakayama
Kenshi
K
Yokoyama
Masayoshi
M
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000601:surgery; D015653:Cystectomy; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D004273:DNA, Neoplasm; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009392:Nephrectomy; D016133:Polymerase Chain Reaction; D017382:Reactive Oxygen Species / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000601:surgery
D004272:DNA, Mitochondrial; D004273:DNA, Neoplasm; D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine