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Cell fusion causes DNA double‐stranded breaks and transformation
Author(s) -
Zhou Xiaofeng,
Cascalho Marilia,
Platt Jeffrey L.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb321
Subject(s) - cell fusion , biology , carcinogenesis , microbiology and biotechnology , mitosis , cell , dna , comet assay , karyotype , chromosomal rearrangement , reprogramming , transformation (genetics) , chromosomal translocation , dna damage , chromosome , genetics , cancer , gene
Cell fusion promotes nuclear reprogramming, tissue repair and regeneration but may also induce tumors. Whether cell fusion drives tumorigenesis on its own is not known. To address this question, we fused rat intestinal epithelial cells (IEC‐6), which have a normal karyotype, exhibit contact inhibition and anchorage dependant growth, using polyethylene glycol and sorted the hybrids by FACS to establish clonal populations. Clones of single diploid IEC‐6 cells were also established as controls. After ten passages, we determined the fraction of fused clones that grew spheres in soft agar, a measure of cell transformation. More than 25% of the fusion‐derived clones were transformed, compared to 1% of non‐fused IEC‐6 clones. Fusion derived cells exhibited chromosome truncation and translocation, suggesting DNA double‐stranded breaks occurred at the outset or early passage. Consistent with this possibility, fusion‐derived cells studied at early passages had a high rate of DNA double‐stranded breaks, as estimated by γH2AX staining and comet assays. We propose that fusion‐induced DNA double‐strand breaks predispose cells to transformation by increasing the frequency of chromosomal rearrangements. These findings implicate cell fusion, as seen in inflammation, tissue injury and repair, in the genesis of tumors. This work is supported by NIH grant 5R37HL052297.