From: Tumor hypoxia as a driving force in genetic instability
Author | % Oxygen | Cell system | Assays | Key findings |
---|---|---|---|---|
Rice et al. [70] | 0% | AA8 (CHO) | Flow cytometry, gene copy analyses | - Anoxia induces S-phase overreplication and increases the frequency of dihydrofolate reductase gene amplification |
Young et al. [71] | 0% (<10Â ppm) | KHT-C2-LP1 (M-fibrosarcoma), | Metastasis assay, flow cytometry | - Anoxia induces DNA overreplication and increases metastatic potential |
B16F10-A1 (M-melanoma) | ||||
Reynolds et al. [61] | 0% (<10 ppm) | LN12 (M-fibroblasts) | Chromosome based λ shuttle vector, PCR, DNA sequence analysis | - Anoxia induces 3–4 fold increase in supF tRNA suppressor gene mutation (transversions and deletions) frequency |
Rofstad et al. [72] | 0% (<10Â ppm and <100Â ppm) | BEX-c (H-melanoma), | Flow cytometry, Giemsa | - Anoxia followed by reoxygenation induces diplochromosomes and tetraploidization |
SAX-c (H-melanoma) | ||||
Coquelle et al. [73] | 0.02% | GMA32 (Chinese hamster fibroblasts) | Fluorescence in situ hybridization (FISH) | - Severe hypoxia induces fragile sites and generates homogeneously stained regions (HSRs) |
Yuan et al. [74] | 0% (<10Â ppm) | 3340 (M-fibroblast) | Host cell reactivation (HCR) assay, UV mutagenesis assay | - Anoxia induces 2-fold increase in supFG1 mutation frequency |
Coquelle et al. [75] | 0.02% | GMA32 (Chinese hamster fibroblasts), 112 (Chinese hamster fibroblasts) | Fluorescence in situ hybridization (FISH) | - Severe hypoxia activates fragile sites and generates double minutes and dicentric chromosomes |
Mihaylova et al. [76] | 0% <10 ppm | 3340 (M-fibroblasts), HeLa (H-cervix adenocarcinoma), EMT6 (M-breast carcinoma) | β-galactosidase and supFG1 mutation assays | - Anoxia induces 2-fold increase in supFG1, cII and lacZ mutation frequency |
Banath et al. [77] | i.p. pimonidazole | V79-VE (Chinese hamster fibroblasts), | Flow cytometry, γ-H2AX foci, HPRT mutation assay, alkaline comet assay | - Hypoxia (cells distant to the blood vessels) followed by reoxygenation does not alter mutation frequency at HPRT locus, DNA strand break rejoining or resolution of γ-H2AX foci following ionizing radiation (IR) |
HCT116 (H-colon carcinoma), | ||||
SCCVII (M-squamous cell carcinoma) | ||||
Koshiji et al. [78] | 1% | HCT116 (H-colon carcinoma), | β-galactosidase mutation assay, microsatellite analysis | - Hypoxia increases the frequency of microsatellite mutations |
HEC59 (H-endometrial carcinoma) | ||||
Papp-Szabo et al. [59] | 0% | ME (R-mammary epithelial cells), | cII mutagenicity assay | - Anoxia increases the mutation frequency by 2-fold at cII locus without affecting colonogenic survival |
MFib (R-mammary fibroblasts) | ||||
Fischer et al. [79] | 0% | TX3868 (H-glioblastoma) | Fluorescence in situ hybridization (FISH) | - Anoxia induces double minutes, fragile sites and anaphase-bridges and initiates gene amplification on chromosome 12q |
Rodriguez-Jimenez et al. [80] | 1% | C17.2 (M-multipotent neural precursor cells), M-primary neurospheres from CD31, BMMSC (H-mesenchymal stem cells), DPSC (H-mesenchymal stem cells) | Host cell reactivation (HCR) assay, microsatellite instability analysis | - Hypoxia increases mutation frequency of the β-galactosidase reporter gene and causes microsatellite instability |
Keysar et al. [60] | <0.1% | AL(N) (CHO) | Complement cytotoxic assay, flow cytometry mutation assay | - Anoxia results in a significant induction of mutations especially large deletions in CD59 gene |
Lee et al. [81] | 3% | Primary lymphocytes from healthy donors | Sister chromatid exchange (SCE) assay, microsatellite instability assay | - Hypoxia increases SCE but does not alter microsatellite instability |
Pires et al. [38] | <0.02% | RKO (H-colon carcinoma), HCT116 (H-colon carcinoma), U2OS (H-osteosarcoma), IBR3 (H-fibroblast) | DNA fiber analysis, immunofluorescence | - Anoxia blocks DNA replication at the initiation and elongation stages and compromises DNA replication restart - Acute anoxia following reoxygenation (cycling hypoxia) does not affect DNA replication restart |
Kumareswaran et al.* [82] | 0.2% | GM05757 (H-fibroblasts) | Giemsa, Multicolor fluorescence in situ hybridization (M-FISH) | - Hypoxia increases the frequency of fragmented DNA, ring chromosomes, telomeric fusions, chromosomal translocations and marker chromosomes following exogenous DNA damage |