Table 3.
Non-exhaustive list of clinical studies using γ-H2AX for diagnostics
| Samples | Details of diagnostics | IR protocol | Assay | Refs. |
|---|---|---|---|---|
| RADIATION TOXICITY | ||||
| Lymphoblastoid cells | Use of γ-H2AX to discriminate cells from individuals carrying the ATM mutation | 0.1Gy/h - 24 h | M | [134] |
| G0 T cells | T cells from AT and NBS patients show impaired elimination of radiation-induced DSBs | 0.5-2Gy at 2Gy/min | FC | [135] |
| G1 Skin fibroblasts | Use of γ-H2AX to show radiation hypersensitivity in cells from parents of RB patients screened as well as in 6 of 15 from apparently normal individuals | 0.5 – 1.0 Gy at 250 cGy/min or 10 cGy/h for 24 h | M | [136] |
| T-and lymphoblastoid cells/PBMCs | Confirmation of radiosensitive A-T patients | 2 Gy | M | [137, 138] |
| PBMCs | Use of γ-H2AX to predict tissue toxicity (mucositis) in patients undergoing head-and-neck radiotherapy | 2 Gy (SD) 60–66 Gy (CD) |
FC | [139] |
| G1 Skin fibroblasts | Use of γ-H2AX to show that cells from Fanconi anemia patients display a significant delay hi the repair of radiation-induced DSBs | 1 Gy (0.45 Gy/min) | M | [140] |
| Fibroblasts | Confirmation of a novel splice variant of the DNA-PKcs gene associated with radiosensitivity | 2Gy | M | [141] |
| PBMCs | Use of γ-H2AX to identify children at risk for radiation toxicity | 1–2 Gy (1 Gy/min) | M | [142] |
| Lymphoblast cell lines | The identification of a patient with a DNA repair defect during a screening for radiosensitivity | 1, 2, 4 Gy (0.62 Gy/min) | M | [86] |
| PBMCs | Use of γ-H2AX to predict excessive normal tissue toxicity in radiotherapy patients | 2 Gy | FC | [88] |
| Blood samples | γ-H2AX as a molecular predictor of prostate cancer radiosensitivity | N/A | N/A | NCT00523471 (#) |
| OTHER DIAGNOSIS | |||
|---|---|---|---|
| Samples | Details of diagnostics | Assay | Refs. |
| Tumor biopsies | γ-H2AX as a potential cancer biomarker | M | [90] |
| Tumor biopsies | Diagnosis for metastatic renal cell carcinoma | M | [92, 143] |
| Colon biopsies | Increased DNA damage in colon of ulcerative colitis patients | M | [99] |
| Melanomas | Evaluation of the γ-H2AX assay as a marker for melauocytic lesions | M | [91] |
| Bladder urothelial carcinoma | Use of γ-H2AX to predict cancer recurrence and/or progression | M | [144] |
| PBMCs | Increased DNA damage and cell death in lymphocytes from patients with occult HBV infections | N/A | [104] |
| Immortalized lymphoblasts | Increased basal DNA damage in cells from individuals with schizophrenia | FC | [106] |
| Lung tissue (alveolar wall cells) | Increased DNA damage levels in lungs of advanced COPD patients | M | [100] |
| Malignant plasma cells | DNA damage escalation during the development of multiple myeloma | M | [95] |
| Fibroblast, T cells | Increased γ-H2AX in lymphocytes and fibroblasts of dyskeratosis congenital patients | M, FC | [102] |
| PBMCs | Increased DNA damage in lymphocytes from obese and overweight children | M | [101] |
| Curettage specimens of endometrial cancer | Use of γ-H2AX as an additional histopathological prognostic parameter in patients with endometrial cancer | M | [145] |
| Squamous epithelia of the uterine cervix | Use of γ-H2AX as a cancer biomarker in patients with cervix cancer | M | [146] |
| N/A | Use of γ-H2AX as a biomarker in women undergoing IVF Treatment | N/A | NCT00685282 (#) |
Abbreviations: M: microscopy (immunocytochemistry or immunohistochemistry); FC: flow cytometry; N/A: not applicable; PBMCs, peripheral blood mononuclear cells; SD, single dose; CD, cumulated doses; (#): ClinicalTrials.gov Identifier