title: Cisplatin selects short forms of the mitochondrial DNA OriB variant (16184-16193 poly-cytosine tract), which confer resistance to cisplatin.
abstract: A 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.
authors.affiliation: Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki 211-8533, Japan.|Department of Applied Chemistry, National Defense Academy, 1-10-20 Hashirimizu, Yokosuka 239-8686, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Amo
authors.affiliation: Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki 211-8533, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Kamimura
authors.affiliation: Department of Applied Chemistry, National Defense Academy, 1-10-20 Hashirimizu, Yokosuka 239-8686, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Asano
authors.affiliation: Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki 211-8533, Japan.
authors.forename: Sadamitsu
authors.initials: S
authors.lastname: Asoh
authors.affiliation: Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki 211-8533, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ohta
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001483:Base Sequence; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D003596:Cytosine / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005472:Fluorouracil / Q000494:pharmacology; D014644:Genetic Variation; D006367:HeLa Cells; D006801:Humans; D006822:Hybrid Cells / Q000187:drug effects / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D017422:Sequence Analysis, DNA
chemical_list: D000970:Antineoplastic Agents; D004272:DNA, Mitochondrial; D003596:Cytosine; D010088:Oxidoreductases; D002945:Cisplatin; D005472:Fluorouracil