粒体DNA片段诱导小鼠胚胎成纤维细胞恶性转化

Malignanttransformation of mouse embryonic fibroblast induced by mitochondrial DNA fragments

Objective　To investigate the malignanttransforming effect and mechanism of mitochondrial DNA (mtDNA) fragments. Methods　Tumorigenicity ofmtDNA-transformed mouse embryonic fibroblast (NIH3T3) in nude mice was studied usingtransgenic techniques. Transformed tumors were detected by pathological examination andhybridization signals of mtDNA probe were analyzed by fluorescence in situ hybridization(FISH) techniques. Results　Hybridization signals were observed on the nuclei of 18%～20% NIH 3T3 cells 1 week aftermtDNA fragments transforming. Tumor from mtDNA-transformed NIH 3T3 cells was developed inall 8 nude mice (8/8) respectively 2 weeks after the transformation. The pathologicalcharacteristics of the tumors developed were similar to that of fibrosarcoma. Conclusions　Auto-integration of mtDNAfragments into nuclear genome is a new factor involved in carcinogenesis.