Premium
Mitochondrial alteration in malignantly transformed human small airway epithelial cells induced by α‐particles
Author(s) -
Zhang Suping,
Wen Gengyun,
Huang Sarah XL,
Wang Jianrong,
Tong Jian,
Hei Tom K.
Publication year - 2012
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.27656
Subject(s) - mitochondrion , biology , mitochondrial dna , carcinogenesis , malignant transformation , neoplastic transformation , telomerase reverse transcriptase , cytochrome c oxidase , microbiology and biotechnology , telomerase , cell growth , phenotype , oxidative phosphorylation , dna damage , cell , dna , cancer research , gene , biochemistry
Human small airway epithelial cells (SAECs) immortalized with human telomerase reverse transcriptase were exposed to either a single or multiple doses of α‐particles. Irradiated cells showed a dose‐dependent cytotoxicity and progressive neoplastic transformation phenotype. These included an increase in saturation density of growth, a greater resistance to N ‐phosphonoacetyl‐ L ‐aspartate, faster anchorage‐independent growth, reinforced cell invasion and c‐Myc expression. In addition, the transformed cells formed progressively growing tumors upon inoculation into athymic nude mice. Specifically, α‐irradiation induced damage to both mitochondrial DNA (mtDNA) and mitochondrial functions in transformed cells as evidenced by increased mtDNA copy number and common deletion, decreased oxidative phosphorylation activity as measured by cytochrome C oxidase (COX) activity and oxygen consumption. There was a linear correlation between mtDNA copy number, common deletion, COX activity and cellular transformation represented by soft agar colony formation and c‐Myc expression. These results suggest that mitochondria are associated with neoplastic transformation of SAEC cells induced by α‐particles, and that the oncogenesis process may depend not only on the genomes inside the nucleus, but also on the mitochondrial DNA outside the nucleus.