Dataset: A transcriptionally induced antioxidant program is elicited in thyroid cells after exposure to hydrogen peroxide
Radiation is an established cause of thyroid cancer and growing evidence supports a role for H2O2 in spontaneous thyroid carcinogenesis....
Radiation is an established cause of thyroid cancer and growing evidence supports a role for H2O2 in spontaneous thyroid carcinogenesis. Little is known about the molecular programs activated by these agents in thyroid cells. We profiled the DNA damage response and cell death induced by γ-radiation (0.1–5Gy) and H2O2 (0.0025–0.3mM) in primary human thyroid cells and T-cells. While the two cell types had more comparable radiation responses, 3- to 10-fold more H2O2 was needed to induce detectable DNA damage in thyrocytes. At H2O2 and radiation doses incurring double-strand breaks (DSB), cell death occurred after 24hrs in T-cells, but not in thyrocytes. We next prepared thyroid and T-cells primary cultures from 8 donors operated for non-cancerous pathologies and profiled their genome-wide transcriptional response 4hr after: 1) exposure to 1 Gy radiation, 2) treatment with H2O2, or 3) no treatment. Two H2O2 doses were investigated, calibrated in each cell type as to elicit levels of single- and double-strand breaks equivalent to 1 Gy γ-radiation. The transcriptional responses of thyrocyte and T-cells to radiation were similar, involving DNA repair and cell death genes. In addition to this transcriptional program, H2O2 also upregulated antioxidant genes in thyrocytes, including glutathione peroxidases (GPx) at the DSB-inducing dose. By contrast, a transcriptional storm involving thousands of genes was raised in T-cells. Finally, we showed that GPx inhibition reduced the DNA damaging effect of H2O2 in thyrocytes. We conjecture that defects of anti- H2O2 protection could promote spontaneous thyroid cancers. Here we characterize the response of thyrocytes to H2O2 from the perspective of DNA damage (SSB and DSB), cell death and genome-wide transcription. We adopted a dual comparative set up. First, in order to gain preliminary insights about which effects are specific to thyrocytes, all experiments were run in parallel in T-cells. Second, all experiments were replicated with radiation, providing a comparison with a proven etiological agent of PTCs. Hence, we investigated all 4 combinations of two factors: thyrocytes vs. T-cells and H2O2 vs. radiation. Cell lines divide indefinitively owning to basic dysfunctions of cell cycle controls. These have the potential to distort the stress response, DNA repair and cell death in particular. Hence, we worked exclusively on human primary cultures. The radiation and presumably also the H2O2 responses vary among individuals. We seek to average out individual effects by replicating the microarray experiments across the matched T-cells and thyrocytes of 8 donors.
- Species:
- human
- Samples:
- 64
- Source:
- E-GEOD-39156
- Updated:
- Dec.12, 2014
- Registered:
- Jul.12, 2014
Sample | AGE YEARS | TSI | ANTI-TG | CD4/CD8 | ANTI-TPO | PURITY | SEX | EXPERIMENT | TREATMENT | CELL COUNT | PATIENT ID | COMET | PATHOLOGY | COMET.SCORE | DATE OF BLOOD TEST DMY | CELLS TYPE |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
GSM957158 | 48 | NA | - | 2.2 | - | 88 | female | J5 | radiation | 146000 | H | 1.49 | isolated cold nodule | 228 | 2010-01-07 | primary T-cells |
GSM957157 | 48 | NA | - | 2.2 | - | 88 | female | J5 | high H2O2 | 146000 | H | 2.52 | isolated cold nodule | 388 | 2010-01-07 | primary T-cells |
GSM957156 | 48 | NA | - | 2.2 | - | 88 | female | J5 | low H2O2 | 146000 | H | 1.32 | isolated cold nodule | 203 | 2010-01-07 | primary T-cells |
GSM957155 | 48 | NA | - | 2.2 | - | 88 | female | J5 | none | 146000 | H | 1 | isolated cold nodule | 154 | 2010-01-07 | primary T-cells |
GSM957154 | 48 | NA | - | 2.2 | - | 88 | female | J5 | radiation | 146000 | H | 1.16 | isolated cold nodule | 129 | 2010-01-07 | primary thyroid cells |
GSM957153 | 48 | NA | - | 2.2 | - | 88 | female | J5 | high H2O2 | 146000 | H | 2.05 | isolated cold nodule | 227 | 2010-01-07 | primary thyroid cells |
GSM957152 | 48 | NA | - | 2.2 | - | 88 | female | J5 | low H2O2 | 146000 | H | 1.06 | isolated cold nodule | 117 | 2010-01-07 | primary thyroid cells |
GSM95715 | 48 | NA | - | 2.2 | - | 88 | female | J5 | none | 146000 | H | 1 | isolated cold nodule | 111 | 2010-01-07 | primary thyroid cells |
GSM957150 | 65 | NA | NA | 3.7 | NA | 92 | female | J6 | radiation | 188000 | G | 1.52 | multinodular goiter | 191 | 2009-12-10 | primary T-cells |
GSM957149 | 65 | NA | NA | 3.7 | NA | 92 | female | J6 | high H2O2 | 188000 | G | 3.08 | multinodular goiter | 389 | 2009-12-10 | primary T-cells |
GSM957148 | 65 | NA | NA | 3.7 | NA | 92 | female | J6 | low H2O2 | 188000 | G | 1.11 | multinodular goiter | 140 | 2009-12-10 | primary T-cells |
GSM957147 | 65 | NA | NA | 3.7 | NA | 92 | female | J6 | none | 188000 | G | 1 | multinodular goiter | 126 | 2009-12-10 | primary T-cells |
GSM957146 | 65 | NA | NA | 3.7 | NA | 92 | female | J6 | radiation | 188000 | G | 1.13 | multinodular goiter | 132 | 2009-12-10 | primary thyroid cells |
GSM957145 | 65 | NA | NA | 3.7 | NA | 92 | female | J6 | high H2O2 | 188000 | G | 1.82 | multinodular goiter | 213 | 2009-12-10 | primary thyroid cells |
GSM957144 | 65 | NA | NA | 3.7 | NA | 92 | female | J6 | low H2O2 | 188000 | G | 1.06 | multinodular goiter | 125 | 2009-12-10 | primary thyroid cells |
GSM957143 | 65 | NA | NA | 3.7 | NA | 92 | female | J6 | none | 188000 | G | 1 | multinodular goiter | 117 | 2009-12-10 | primary thyroid cells |
GSM957142 | 21 | + | + | 2.6 | + | 92 | female | J6 | radiation | 154000 | F | 1.03 | Graves' disease | 136 | 2010-01-13 | primary T-cells |
GSM95714 | 21 | + | + | 2.6 | + | 92 | female | J6 | high H2O2 | 154000 | F | 2.97 | Graves' disease | 394 | 2010-01-13 | primary T-cells |
GSM957140 | 21 | + | + | 2.6 | + | 92 | female | J6 | low H2O2 | 154000 | F | 1.52 | Graves' disease | 202 | 2010-01-13 | primary T-cells |
GSM957139 | 21 | + | + | 2.6 | + | 92 | female | J6 | none | 154000 | F | 1 | Graves' disease | 133 | 2010-01-13 | primary T-cells |
GSM957138 | 21 | + | + | 2.6 | + | 92 | female | J6 | radiation | 154000 | F | 1.09 | Graves' disease | 128 | 2010-01-13 | primary thyroid cells |
GSM957137 | 21 | + | + | 2.6 | + | 92 | female | J6 | high H2O2 | 154000 | F | 2.13 | Graves' disease | 249 | 2010-01-13 | primary thyroid cells |
GSM957136 | 21 | + | + | 2.6 | + | 92 | female | J6 | low H2O2 | 154000 | F | 1.08 | Graves' disease | 127 | 2010-01-13 | primary thyroid cells |
GSM957135 | 21 | + | + | 2.6 | + | 92 | female | J6 | none | 154000 | F | 1 | Graves' disease | 117 | 2010-01-13 | primary thyroid cells |
GSM957134 | 50 | NA | - | 3.2 | - | 93 | male | J6 | radiation | 106000 | E | 1.07 | Isolated cold nodule | 219 | 2009-12-08 | primary T-cells |
GSM957133 | 50 | NA | - | 3.2 | - | 93 | male | J6 | high H2O2 | 106000 | E | 1.94 | Isolated cold nodule | 395 | 2009-12-08 | primary T-cells |
GSM957132 | 50 | NA | - | 3.2 | - | 93 | male | J6 | low H2O2 | 106000 | E | 1.2 | Isolated cold nodule | 245 | 2009-12-08 | primary T-cells |
GSM95713 | 50 | NA | - | 3.2 | - | 93 | male | J6 | none | 106000 | E | 1 | Isolated cold nodule | 204 | 2009-12-08 | primary T-cells |
GSM957130 | 50 | NA | - | 3.2 | - | 93 | male | J6 | radiation | 106000 | E | 0.94 | Isolated cold nodule | 127 | 2009-12-08 | primary thyroid cells |
GSM957129 | 50 | NA | - | 3.2 | - | 93 | male | J6 | high H2O2 | 106000 | E | 1.91 | Isolated cold nodule | 257 | 2009-12-08 | primary thyroid cells |
GSM957128 | 50 | NA | - | 3.2 | - | 93 | male | J6 | low H2O2 | 106000 | E | 0.88 | Isolated cold nodule | 119 | 2009-12-08 | primary thyroid cells |
GSM957127 | 50 | NA | - | 3.2 | - | 93 | male | J6 | none | 106000 | E | 1 | Isolated cold nodule | 135 | 2009-12-08 | primary thyroid cells |
GSM957126 | 60 | NA | - | 3.6 | - | 91 | female | J5 | radiation | 123000 | D | 1.13 | multinodular goiter | 139 | 2009-10-19 | primary T-cells |
GSM957125 | 60 | NA | - | 3.6 | - | 91 | female | J5 | high H2O2 | 123000 | D | 3.26 | multinodular goiter | 399 | 2009-10-19 | primary T-cells |
GSM957124 | 60 | NA | - | 3.6 | - | 91 | female | J5 | low H2O2 | 123000 | D | 1.31 | multinodular goiter | 160 | 2009-10-19 | primary T-cells |
GSM957123 | 60 | NA | - | 3.6 | - | 91 | female | J5 | none | 123000 | D | 1 | multinodular goiter | 123 | 2009-10-19 | primary T-cells |
GSM957122 | 60 | NA | - | 3.6 | - | 91 | female | J5 | radiation | 123000 | D | 1 | multinodular goiter | 110 | 2009-10-19 | primary thyroid cells |
GSM95712 | 60 | NA | - | 3.6 | - | 91 | female | J5 | high H2O2 | 123000 | D | 2.79 | multinodular goiter | 306 | 2009-10-19 | primary thyroid cells |
GSM957120 | 60 | NA | - | 3.6 | - | 91 | female | J5 | low H2O2 | 123000 | D | 1 | multinodular goiter | 110 | 2009-10-19 | primary thyroid cells |
GSM957119 | 60 | NA | - | 3.6 | - | 91 | female | J5 | none | 123000 | D | 1 | multinodular goiter | 110 | 2009-10-19 | primary thyroid cells |
GSM957118 | 53 | NA | NA | 2.1 | NA | 90 | female | J6 | radiation | 253000 | C | 0.98 | multinodular thyroid | 153 | 2009-11-30 | primary T-cells |
GSM957117 | 53 | NA | NA | 2.1 | NA | 90 | female | J6 | high H2O2 | 253000 | C | 2.52 | multinodular thyroid | 392 | 2009-11-30 | primary T-cells |
GSM957116 | 53 | NA | NA | 2.1 | NA | 90 | female | J6 | low H2O2 | 253000 | C | 1.04 | multinodular thyroid | 162 | 2009-11-30 | primary T-cells |
GSM957115 | 53 | NA | NA | 2.1 | NA | 90 | female | J6 | none | 253000 | C | 1 | multinodular thyroid | 156 | 2009-11-30 | primary T-cells |
GSM957114 | 53 | NA | NA | 2.1 | NA | 90 | female | J6 | radiation | 253000 | C | 1.03 | multinodular thyroid | 116 | 2009-11-30 | primary thyroid cells |
GSM957113 | 53 | NA | NA | 2.1 | NA | 90 | female | J6 | high H2O2 | 253000 | C | 2.3 | multinodular thyroid | 260 | 2009-11-30 | primary thyroid cells |
GSM957112 | 53 | NA | NA | 2.1 | NA | 90 | female | J6 | low H2O2 | 253000 | C | 1.18 | multinodular thyroid | 134 | 2009-11-30 | primary thyroid cells |
GSM957 | 53 | NA | NA | 2.1 | NA | 90 | female | J6 | none | 253000 | C | 1 | multinodular thyroid | 113 | 2009-11-30 | primary thyroid cells |
GSM957110 | 45 | - | - | 2.5 | - | 94 | male | J5 | radiation | 204000 | B | 1.08 | multinodular goiter | 194 | 2009-11-16 | primary T-cells |
GSM957109 | 45 | - | - | 2.5 | - | 94 | male | J5 | high H2O2 | 204000 | B | 2.18 | multinodular goiter | 391 | 2009-11-16 | primary T-cells |
GSM957108 | 45 | - | - | 2.5 | - | 94 | male | J5 | low H2O2 | 204000 | B | 1.03 | multinodular goiter | 185 | 2009-11-16 | primary T-cells |
GSM957107 | 45 | - | - | 2.5 | - | 94 | male | J5 | none | 204000 | B | 1 | multinodular goiter | 179 | 2009-11-16 | primary T-cells |
GSM957106 | 45 | - | - | 2.5 | - | 94 | male | J5 | radiation | 204000 | B | 1.01 | multinodular goiter | 116 | 2009-11-16 | primary thyroid cells |
GSM957105 | 45 | - | - | 2.5 | - | 94 | male | J5 | high H2O2 | 204000 | B | 2.03 | multinodular goiter | 232 | 2009-11-16 | primary thyroid cells |
GSM957104 | 45 | - | - | 2.5 | - | 94 | male | J5 | low H2O2 | 204000 | B | 1.04 | multinodular goiter | 119 | 2009-11-16 | primary thyroid cells |
GSM957103 | 45 | - | - | 2.5 | - | 94 | male | J5 | none | 204000 | B | 1 | multinodular goiter | 114 | 2009-11-16 | primary thyroid cells |
GSM957102 | 40 | - | - | 2.2 | + | 84 | male | J5 | radiation | 200000 | A | 1.08 | Graves' disease | 145 | 2010-02-12 | primary T-cells |
GSM95710 | 40 | - | - | 2.2 | + | 84 | male | J5 | high H2O2 | 200000 | A | 2.93 | Graves' disease | 393 | 2010-02-12 | primary T-cells |
GSM957100 | 40 | - | - | 2.2 | + | 84 | male | J5 | low H2O2 | 200000 | A | 1.15 | Graves' disease | 154 | 2010-02-12 | primary T-cells |
GSM957099 | 40 | - | - | 2.2 | + | 84 | male | J5 | none | 200000 | A | 1 | Graves' disease | 134 | 2010-02-12 | primary T-cells |
GSM957098 | 40 | - | - | 2.2 | + | 84 | male | J5 | radiation | 200000 | A | 1.13 | Graves' disease | 171 | 2010-02-12 | primary thyroid cells |
GSM957097 | 40 | - | - | 2.2 | + | 84 | male | J5 | high H2O2 | 200000 | A | 1.94 | Graves' disease | 292 | 2010-02-12 | primary thyroid cells |
GSM957096 | 40 | - | - | 2.2 | + | 84 | male | J5 | low H2O2 | 200000 | A | 0.91 | Graves' disease | 137 | 2010-02-12 | primary thyroid cells |
GSM957095 | 40 | - | - | 2.2 | + | 84 | male | J5 | none | 200000 | A | 1 | Graves' disease | 151 | 2010-02-12 | primary thyroid cells |