Cisplatin selects short forms of the mitochondrial DNA OriB variant (16184–16193 poly-cytosine tract), which confer resistance to cisplatin
Copyright policy )Cisplatin selects short forms of the mitochondrial DNA OriB variant (16184–16193 poly-cytosine tract), which confer resistance to cisplatin
AbstractA number of alternations in mitochondrial DNA (mtDNA) have been reported in different types of cancers, and the role of mtDNA in cancer has been attracting increasing interest. In order to investigate the relationship between mtDNA alternations and chemosensitivity, we constructed cybrid (trans-mitochondrial hybrid) cell lines carrying a HeLa nucleus and the mtDNA of healthy individuals because of the presence of somatic alternations in the mtDNA of many cancer cells. After a treatment with 1.0 μg/mL cisplatin for 10 days, we isolated 100 cisplatin-resistant clones, 70 of which carried the shorter mtDNA OriB variant (16184–16193 poly-cytosine tract), which was located in the control region of mtDNA. Whole mtDNA sequencing of 10 clones revealed no additional alternations. Re-construction of the HeLa nucleus and mtDNA from cisplatin-resistant cells showed that cisplatin resistance was only acquired by mtDNA alternations in the control region, and not by possible alternation(s) in the nuclear genome.
- Nippon Medical School Japan
- National Defence Academy India
- National Defense Academy of Japan Japan
- Hitachi (Japan) Japan
Base Sequence, Cell Survival, Genetic Variation, Antineoplastic Agents, Cell Separation, Sequence Analysis, DNA, Hybrid Cells, DNA, Mitochondrial, Article, Cytosine, Drug Resistance, Neoplasm, Humans, Fluorouracil, Cisplatin, Oxidoreductases, HeLa Cells
Base Sequence, Cell Survival, Genetic Variation, Antineoplastic Agents, Cell Separation, Sequence Analysis, DNA, Hybrid Cells, DNA, Mitochondrial, Article, Cytosine, Drug Resistance, Neoplasm, Humans, Fluorouracil, Cisplatin, Oxidoreductases, HeLa Cells
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