Table 1.
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% (<10 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% (<10 ppm and <100 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% (<10 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 |
CHO – Chinese hamster ovary cells; M – mouse; H – human; R – rat.
*only study investigating DNA repair under continual hypoxic conditions.