Polymorphic mutations in mouse mitochondrial DNA regulate a tumor phenotype.
To examine whether polymorphic mtDNA mutations that do not induce significant respiration defects regulate phenotypes of tumor cells, we used mouse transmitochondrial tumor cells (cybrids) with nuclear DNA from C57BL/6 (B6) strain and mtDNA from allogenic C3H strain. The results showed that polymorphic mutations of C3H mtDNA in the cybrids induced hypoxia sensitivity, resulting in a delay of tumor formation on their subcutaneous inoculation into B6 mice. Therefore, the effects of polymorphic mutations in normal mtDNA have to be carefully considered, particularly when we apply the gene therapy to the embryos to replace their pathogenic mtDNA by normal mtDNA.
Faculty of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan.
Gaku
G
Takibuchi
Hirotake
H
Imanishi
Mami
M
Morimoto
Kaori
K
Ishikawa
Kazuto
K
Nakada
Noriko
N
Toyama-Sorimachi
Yoshiaki
Y
Kikkawa
Keizo
K
Takenaga
Jun-Ichi
J
Hayashi
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D004272:DNA, Mitochondrial / Q000235:genetics*; D004591:Electrophoresis, Polyacrylamide Gel; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009154:Mutation; D009374:Neoplasms, Experimental / Q000235:genetics*; D011110:Polymorphism, Genetic; D017382:Reactive Oxygen Species
D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D000111:Acetylcysteine
Hypoxia sensitivity; Mouse C3H mtDNA; Polymorphic mtDNA mutations; Transmitochondrial cybrids; Tumor phenotypes