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Shanaz A. Ghandhi, Helen C. Turner, Igor Shuryak, Gregory O. Dugan, J. Daniel Bourland, John D. Olson, Janet A. Tooze, Shad R. Morton, Ines Batinic-Haberle, J. Mark Cline, Sally A. Amundson
Whole thorax irradiation of non-human primates induces persistent nuclear damage and gene expression changes in peripheral blood cells
www.plosone.org
www.plosone.org
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239.3575 407.3386 l
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f*
244.5165 407.3386 m
254.0409 407.3386 l
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f*
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269.4614 368.3339 l
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f*
273.8268 368.3339 m
283.2945 368.3339 l
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287.6598 368.3339 m
297.1843 368.3339 l
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(20)Tj
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(22)Tj
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(21)Tj
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0 0 Td
(Peripheral)Tj
4.3596 0 Td
(blood)Tj
2.5172 0 Td
(samples)Tj
3.3788 0 Td
(\(~)Tj
1.1396 0 Td
(1)Tj
0.6973 0 Td
(mL\))Tj
1.9162 0 Td
(were)Tj
2.126 0 Td
(collected)Tj
3.736 0 Td
(in)Tj
1.0375 0 Td
(lithium-heparin)Tj
6.616 0 Td
(vacutainer)Tj
4.3993 0 Td
(tubes)Tj
2.3414 0 Td
(\(Bec-)Tj
-34.2649 -1.3039 Td
(ton-Dickson,)Tj
5.4878 0 Td
(Franklin)Tj
3.6623 0 Td
(Lakes,)Tj
2.6986 0 Td
(New)Tj
2.0636 0 Td
(Jersey\))Tj
2.9197 0 Td
(and)Tj
1.7348 0 Td
(PAXgene)Tj
3.9741 0 Td
(RNA)Tj
2.262 0 Td
(stabilization)Tj
5.0684 0 Td
(tubes)Tj
2.3357 0 Td
(\(PreAnalytix,)Tj
-32.207 -1.2982 Td
(Qiagen,)Tj
3.3278 0 Td
(catalog)Tj
3.0274 0 Td
(number)Tj
3.4185 0 Td
(762165\).)Tj
3.6397 0 Td
(For)Tj
1.6271 0 Td
(the)Tj
1.4683 0 Td
(micronucleus)Tj
5.6693 0 Td
(assay,)Tj
2.4888 0 Td
(blood)Tj
2.5115 0 Td
(was)Tj
1.7007 0 Td
(collected)Tj
3.7417 0 Td
(over)Tj
1.9729 0 Td
(the)Tj
-34.5937 -1.2983 Td
(8-month)Tj
3.7473 0 Td
(study)Tj
2.3868 0 Td
(period)Tj
2.8346 0 Td
(\(Days)Tj
2.5455 0 Td
(-3,)Tj
1.2756 0 Td
(2,)Tj
0.9184 0 Td
(5,)Tj
0.9184 0 Td
(37,)Tj
1.4003 0 Td
(66,)Tj
1.3947 0 Td
(93,)Tj
1.3946 0 Td
(123,)Tj
1.8765 0 Td
(151,)Tj
1.8709 0 Td
(186)Tj
1.6441 0 Td
(and)Tj
1.7348 0 Td
(249\).)Tj
2.211 0 Td
(Fresh)Tj
2.4321 0 Td
(blood)Tj
2.5115 0 Td
(samples)Tj
-33.0971 -1.3039 Td
(were)Tj
2.1203 0 Td
(shipped)Tj
3.3618 0 Td
(FedEx)Tj
2.7326 0 Td
(priority)Tj
3.2768 0 Td
(overnight)Tj
4.0819 0 Td
(at)Tj
0.9524 0 Td
(ambient)Tj
3.5206 0 Td
(temperature)Tj
5.125 0 Td
(to)Tj
1.0262 0 Td
(the)Tj
1.4683 0 Td
(Center)Tj
2.948 0 Td
(for)Tj
1.389 0 Td
(Radiological)Tj
-32.0029 -1.2983 Td
(Research,)Tj
4.0308 0 Td
(Columbia)Tj
4.1896 0 Td
(University)Tj
4.405 0 Td
(Medical)Tj
3.4356 0 Td
(Center,)Tj
3.1747 0 Td
(New)Tj
2.0636 0 Td
(York,)Tj
2.4492 0 Td
(NY.)Tj
1.8141 0 Td
(During)Tj
3.1351 0 Td
(the)Tj
1.4684 0 Td
(winter)Tj
2.8176 0 Td
(months,)Tj
3.5036 0 Td
(a)Tj
-36.4873 -1.2982 Td
(heat)Tj
1.8992 0 Td
(pack)Tj
2.0806 0 Td
(was)Tj
1.6951 0 Td
(included)Tj
3.7077 0 Td
(with)Tj
1.9899 0 Td
(the)Tj
1.4626 0 Td
(blood)Tj
2.5115 0 Td
(shipment.)Tj
4.2009 0 Td
(Blood)Tj
2.5852 0 Td
(differentials)Tj
4.955 0 Td
(were)Tj
2.1203 0 Td
(measured)Tj
4.0988 0 Td
(from)Tj
2.1997 0 Td
(sepa-)Tj
-35.5065 -1.304 Td
(rate)Tj
1.7461 0 Td
(EDTA)Tj
2.8233 0 Td
(tubes)Tj
2.3357 0 Td
(\(Becton-Dickinson\))Tj
8.1864 0 Td
(collected)Tj
3.7417 0 Td
(pre-irradiation)Tj
6.1738 0 Td
(\(at)Tj
1.2926 0 Td
(191)Tj
1.6441 0 Td
(and)Tj
1.7348 0 Td
(72)Tj
1.1679 0 Td
(days)Tj
2.0012 0 Td
(before)Tj
2.7383 0 Td
(irra-)Tj
-35.5859 -1.2982 Td
(diation\),)Tj
3.6339 0 Td
(and)Tj
1.7292 0 Td
(again)Tj
2.3697 0 Td
(at)Tj
0.9524 0 Td
(9)Tj
0.6974 0 Td
(days)Tj
1.9955 0 Td
(post-irradiation,)Tj
6.7748 0 Td
(and)Tj
1.7291 0 Td
(then)Tj
2.0183 0 Td
(approximately)Tj
5.9754 0 Td
(weekly)Tj
2.948 0 Td
(from)Tj
2.2053 0 Td
(this)Tj
1.6725 0 Td
(time)Tj
-34.7015 -1.2983 Td
(point)Tj
2.3584 0 Td
(until)Tj
2.1089 0 Td
(4)Tj
0.6917 0 Td
(months)Tj
3.2825 0 Td
(post-irradiation,)Tj
6.7747 0 Td
(at)Tj
0.9525 0 Td
(which)Tj
2.6475 0 Td
(time)Tj
2.0296 0 Td
(blood)Tj
2.5172 0 Td
(counts)Tj
2.8856 0 Td
(were)Tj
2.1203 0 Td
(measured)Tj
4.1102 0 Td
(once)Tj
2.1203 0 Td
(a)Tj
-34.5994 -1.2983 Td
(month)Tj
2.9196 0 Td
(until)Tj
2.109 0 Td
(8)Tj
0.6973 0 Td
(months.)Tj
3.5036 0 Td
(Total)Tj
2.3187 0 Td
(and)Tj
1.7291 0 Td
(differential)Tj
4.6035 0 Td
(blood)Tj
2.5171 0 Td
(counts)Tj
2.8857 0 Td
(were)Tj
2.1203 0 Td
(done)Tj
2.228 0 Td
(by)Tj
1.1792 0 Td
(a)Tj
0.6576 0 Td
(veterinary)Tj
4.2633 0 Td
(reference)Tj
-33.732 -1.3039 Td
(laboratory)Tj
4.3483 0 Td
(\(IDEXX,)Tj
3.736 0 Td
(North)Tj
2.6646 0 Td
(Grafton,)Tj
3.6056 0 Td
(MA\).)Tj
2.3641 0 Td
(Analyses)Tj
3.7304 0 Td
(of)Tj
1.0148 0 Td
(blood)Tj
2.5171 0 Td
(cell)Tj
1.559 0 Td
(counts)Tj
2.8857 0 Td
(were)Tj
2.1203 0 Td
(performed)Tj
4.473 0 Td
(by)Tj
-35.0189 -1.2982 Td
(using)Tj
2.3867 0 Td
(the)Tj
1.4683 0 Td
(Dunnett's)Tj
4.1783 0 Td
(method)Tj
3.3278 0 Td
(to)Tj
1.0205 0 Td
(adjust)Tj
2.6305 0 Td
(for)Tj
1.3833 0 Td
(comparison)Tj
4.9776 0 Td
(of)Tj
1.0148 0 Td
(all)Tj
1.1452 0 Td
(times)Tj
2.3925 0 Td
(to)Tj
1.0204 0 Td
(the)Tj
1.474 0 Td
(baseline.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 494.022 cm
BT
/F13 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Micronucleus)Tj
5.9008 0 Td
(assay)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 477.0141 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Whole)Tj
2.8913 0 Td
(blood)Tj
2.5115 0 Td
(samples)Tj
3.3845 0 Td
(\(~)Tj
1.1395 0 Td
(1)Tj
0.6973 0 Td
(mL\))Tj
1.9162 0 Td
(were)Tj
2.1203 0 Td
(diluted)Tj
3.0388 0 Td
(with)Tj
1.9955 0 Td
(5)Tj
0.6974 0 Td
(mL)Tj
1.5817 0 Td
(of)Tj
1.0148 0 Td
(RPMI-1640)Tj
4.8812 0 Td
(medium)Tj
3.6057 0 Td
(\(Invitrogen,)Tj
-31.4757 -1.2982 Td
(Eugene,)Tj
3.4015 0 Td
(OR\).)Tj
2.1543 0 Td
(The)Tj
1.7802 0 Td
(diluted)Tj
3.0387 0 Td
(blood)Tj
2.5171 0 Td
(mixtures)Tj
3.7531 0 Td
(were)Tj
2.1203 0 Td
(layered)Tj
3.1011 0 Td
(over)Tj
1.9785 0 Td
(an)Tj
1.2019 0 Td
(equal)Tj
2.3584 0 Td
(volume)Tj
3.1975 0 Td
(of)Tj
1.0148 0 Td
(lymphocyte)Tj
-31.6174 -1.2983 Td
(separation)Tj
4.3823 0 Td
(media)Tj
2.6929 0 Td
(\(Histopaque-1083;)Tj
7.6478 0 Td
(Invitrogen\);)Tj
5.006 0 Td
(then)Tj
2.0182 0 Td
(centrifuged)Tj
4.7849 0 Td
(at)Tj
0.9524 0 Td
(1300)Tj
2.126 0 Td
(rpm)Tj
1.9275 0 Td
(for)Tj
1.3833 0 Td
(30)Tj
1.1736 0 Td
(minutes.)Tj
-34.0949 -1.2982 Td
(The)Tj
1.7801 0 Td
(lymphocytes)Tj
5.2554 0 Td
(formed)Tj
3.1578 0 Td
(at)Tj
0.9524 0 Td
(the)Tj
1.4683 0 Td
(interface)Tj
3.6964 0 Td
(between)Tj
3.5319 0 Td
(the)Tj
1.4684 0 Td
(separation)Tj
4.3823 0 Td
(medium)Tj
3.6057 0 Td
(were)Tj
2.1203 0 Td
(collected)Tj
3.7417 0 Td
(using)Tj
-35.1607 -1.304 Td
(a)Tj
0.6519 0 Td
(glass)Tj
2.0863 0 Td
(pipette)Tj
2.965 0 Td
(and)Tj
1.7348 0 Td
(then)Tj
2.0183 0 Td
(washed)Tj
3.1748 0 Td
(with)Tj
1.9955 0 Td
(1)Tj
0.6973 0 Td
(X)Tj
0.8731 0 Td
(phosphate)Tj
4.337 0 Td
(buffered)Tj
3.5716 0 Td
(saline)Tj
2.5002 0 Td
(\(PBS\).)Tj
2.7439 0 Td
(The)Tj
1.7801 0 Td
(cells)Tj
1.9219 0 Td
(were)Tj
2.1203 0 Td
(trans-)Tj
-35.172 -1.2982 Td
(ferred)Tj
2.6248 0 Td
(to)Tj
1.0262 0 Td
(12-well)Tj
3.118 0 Td
(multi-well)Tj
4.3314 0 Td
(tissue)Tj
2.4604 0 Td
(culture)Tj
3.0387 0 Td
(plates)Tj
2.5002 0 Td
(\(Becton,)Tj
3.5659 0 Td
(Dickinson)Tj
4.3767 0 Td
(and)Tj
1.7291 0 Td
(Company,)Tj
4.388 0 Td
(Franklin)Tj
-33.1594 -1.2983 Td
(Lakes,)Tj
2.6985 0 Td
(NJ\))Tj
1.6271 0 Td
(containing)Tj
4.5241 0 Td
(5)Tj
0.6973 0 Td
(mL)Tj
1.576 0 Td
(pre-warmed)Tj
5.142 0 Td
(RPMI-1640)Tj
4.8869 0 Td
(medium)Tj
3.6057 0 Td
(supplemented)Tj
5.8563 0 Td
(with)Tj
1.9956 0 Td
(15%)Tj
1.9276 0 Td
(heat-)Tj
-34.5371 -1.3039 Td
(inactivated)Tj
4.5977 0 Td
(fetal)Tj
1.9106 0 Td
(calf)Tj
1.61 0 Td
(serum)Tj
2.7213 0 Td
(\(Invitrogen\),)Tj
5.3517 0 Td
(2%)Tj
1.4514 0 Td
(Pen/Strep)Tj
4.1669 0 Td
(\(10,000)Tj
3.1634 0 Td
(units/mL)Tj
3.9118 0 Td
(penicillin)Tj
3.9742 0 Td
(and)Tj
-32.859 -1.2983 Td
(10,000)Tj
/F15 1 Tf
2.8232 0 Td
[()]TJ
/F7 1 Tf
(g/mL)Tj
2.88 0 Td
(streptomycin;)Tj
5.7316 0 Td
(Invitrogen\))Tj
4.7849 0 Td
(and)Tj
1.7348 0 Td
(2%)Tj
1.4513 0 Td
(phytohaemagglutinin)Tj
8.7987 0 Td
(\(PHA;)Tj
2.7949 0 Td
(Invitrogen\).)Tj
-29.8032 -1.2982 Td
(Cells)Tj
2.1599 0 Td
(were)Tj
2.126 0 Td
(cultured)Tj
3.566 0 Td
(at)Tj
0.9524 0 Td
(37C)Tj
2.228 0 Td
(in)Tj
1.0318 0 Td
(a)Tj
0.6577 0 Td
(humidified)Tj
4.6601 0 Td
(atmosphere)Tj
4.9039 0 Td
(with)Tj
1.9956 0 Td
(5%)Tj
1.457 0 Td
(CO)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 483.4204 358.3559 cm
BT
/F7 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(2)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 486.9921 360.0566 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(.)Tj
0.4478 0 Td
(After)Tj
2.2847 0 Td
(44)Tj
1.1679 0 Td
(hours)Tj
2.5171 0 Td
(of)Tj
-35.1152 -1.3039 Td
(incubation,)Tj
4.7735 0 Td
(cytochalasin)Tj
5.142 0 Td
(B)Tj
0.805 0 Td
(\(Cyt-B,)Tj
3.1295 0 Td
(catalog)Tj
3.0274 0 Td
(number)Tj
3.4185 0 Td
(C6762,)Tj
3.0104 0 Td
(Sigma;)Tj
2.9083 0 Td
(stock)Tj
2.3074 0 Td
(solution)Tj
3.4808 0 Td
(3000)Tj
/F15 1 Tf
2.1203 0 Td
[()]TJ
/F7 1 Tf
(g/mL)Tj
-34.1231 -1.2982 Td
(dissolved)Tj
3.8948 0 Td
(in)Tj
1.0374 0 Td
(dimethylsulphoxide;)Tj
8.3792 0 Td
(Sigma,)Tj
2.9083 0 Td
(St.)Tj
1.2189 0 Td
(Louis,)Tj
2.6476 0 Td
(MO\))Tj
2.1996 0 Td
(was)Tj
1.6951 0 Td
(added)Tj
2.6646 0 Td
(to)Tj
1.0204 0 Td
(the)Tj
1.474 0 Td
(culture)Tj
3.0387 0 Td
(medium)Tj
3.6056 0 Td
(at)Tj
0.9468 0 Td
(a)Tj
-36.731 -1.2983 Td
(final)Tj
2.0012 0 Td
(concentration)Tj
5.8224 0 Td
(of)Tj
1.0147 0 Td
(6)Tj
/F15 1 Tf
0.6917 0 Td
[()]TJ
/F7 1 Tf
(g/mL.)Tj
3.1067 0 Td
(Cells)Tj
2.16 0 Td
(were)Tj
2.1203 0 Td
(cultured)Tj
3.5717 0 Td
(for)Tj
1.3833 0 Td
(an)Tj
1.2018 0 Td
(additional)Tj
4.2803 0 Td
(26)Tj
1.1679 0 Td
(hours)Tj
2.5171 0 Td
(to)Tj
1.0261 0 Td
(arrest)Tj
2.4775 0 Td
(cytoki-)Tj
-34.5427 -1.3039 Td
(nesis)Tj
2.177 0 Td
(and)Tj
1.7348 0 Td
(induce)Tj
2.9366 0 Td
(the)Tj
1.4684 0 Td
(formation)Tj
4.2633 0 Td
(of)Tj
1.0148 0 Td
(once-divided)Tj
5.4651 0 Td
(bi-nucleated)Tj
5.1987 0 Td
(cells.)Tj
2.1487 0 Td
(To)Tj
1.3379 0 Td
(harvest)Tj
3.0897 0 Td
(lymphocytes,)Tj
-30.835 -1.2983 Td
(samples)Tj
3.3789 0 Td
(were)Tj
2.1259 0 Td
(transferred)Tj
4.6375 0 Td
(to)Tj
1.0261 0 Td
(a)Tj
0.652 0 Td
(15)Tj
1.1735 0 Td
(mL)Tj
1.5761 0 Td
(tube)Tj
1.9785 0 Td
(and)Tj
1.7292 0 Td
(centrifuged)Tj
4.7848 0 Td
(at)Tj
0.9524 0 Td
(1,000)Tj
2.3471 0 Td
(rpm)Tj
1.9276 0 Td
(for)Tj
1.3888 0 Td
(10)Tj
1.1679 0 Td
(minutes)Tj
3.4696 0 Td
(and)Tj
1.7291 0 Td
(the)Tj
-36.045 -1.2982 Td
(supernatant)Tj
4.9833 0 Td
(discarded.)Tj
4.3086 0 Td
(The)Tj
1.7801 0 Td
(pelleted)Tj
3.3279 0 Td
(cells)Tj
1.9219 0 Td
(in)Tj
1.0318 0 Td
(the)Tj
1.474 0 Td
(tube)Tj
1.9729 0 Td
(were)Tj
2.1259 0 Td
(treated)Tj
2.9934 0 Td
(for)Tj
1.389 0 Td
(10)Tj
1.1678 0 Td
(minutes)Tj
3.4695 0 Td
(with)Tj
1.9956 0 Td
(cold)Tj
-33.9417 -1.2983 Td
(hypotonic)Tj
4.2689 0 Td
(solution)Tj
3.481 0 Td
(\(0.075)Tj
2.6928 0 Td
(M)Tj
1.1112 0 Td
(KCl,)Tj
2.0296 0 Td
(Sigma-Aldrich,)Tj
6.3042 0 Td
(St.)Tj
1.2189 0 Td
(Louis,)Tj
2.6476 0 Td
(MO\))Tj
2.1996 0 Td
(and)Tj
1.7292 0 Td
(fixed)Tj
2.1882 0 Td
(twice)Tj
2.3187 0 Td
(with)Tj
1.9956 0 Td
(ice-cold)Tj
-34.1855 -1.3039 Td
(fixative)Tj
3.1181 0 Td
(\(methanol:)Tj
4.5864 0 Td
(glacial)Tj
2.7382 0 Td
(acetic)Tj
2.4889 0 Td
(acid::)Tj
2.3243 0 Td
(3:1\))Tj
1.7348 0 Td
(and)Tj
1.7348 0 Td
(then)Tj
2.0183 0 Td
(stored)Tj
2.7042 0 Td
(at)Tj
0.9525 0 Td
(4C)Tj
1.7518 0 Td
(in)Tj
1.0374 0 Td
(a)Tj
0.652 0 Td
(fireproof)Tj
3.7586 0 Td
(refrigerator.)Tj
-31.6003 -1.2983 Td
(Prior)Tj
2.296 0 Td
(to)Tj
1.0262 0 Td
(slide)Tj
2.0409 0 Td
(preparation,)Tj
5.1363 0 Td
(the)Tj
1.4684 0 Td
(lymphocytes)Tj
5.2554 0 Td
(were)Tj
2.1203 0 Td
(centrifuged,)Tj
5.0116 0 Td
(supernatant)Tj
4.9832 0 Td
(discarded)Tj
4.0818 0 Td
(and)Tj
1.7348 0 Td
(resus-)Tj
-35.1549 -1.2983 Td
(pended)Tj
3.1861 0 Td
(in)Tj
1.0375 0 Td
(~0.5)Tj
1.9785 0 Td
(mL)Tj
1.5761 0 Td
(of)Tj
1.0148 0 Td
(fresh)Tj
2.1883 0 Td
(fixative.)Tj
3.3449 0 Td
(A)Tj
0.9071 0 Td
(small)Tj
2.3244 0 Td
(drop)Tj
2.1429 0 Td
(of)Tj
1.0148 0 Td
(lymphocyte)Tj
4.8926 0 Td
(suspension)Tj
4.643 0 Td
(was)Tj
1.7008 0 Td
(transferred)Tj
4.6375 0 Td
(to)Tj
-36.5893 -1.3039 Td
(a)Tj
0.6519 0 Td
(clean)Tj
2.2961 0 Td
(glass)Tj
2.0863 0 Td
(slide;)Tj
2.2733 0 Td
(then)Tj
2.0183 0 Td
(allowed)Tj
3.2882 0 Td
(to)Tj
1.0261 0 Td
(air)Tj
1.2926 0 Td
(dry)Tj
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Q
q
1 j
1 J
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11.9999 0 0 11.9999 200.0125 496.2897 cm
BT
/F13 1 Tf
1 TL
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4.3086 0 Td
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Q
q
1 j
1 J
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BT
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1 TL
-0.004 Tc
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1.61 0 Td
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3.8041 0 Td
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(\(cDNA\))Tj
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1.457 0 Td
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5.76 0 Td
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(CA\).)Tj
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(RT-PCR)Tj
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(\(qRT-PCR\))Tj
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Q
q
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1 J
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7.4999 0 0 6.6659 390.8976 457.7385 cm
BT
/F16 1 Tf
1 TL
-0.0053 Tc
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(1)Tj
ET
Q
q
1 j
1 J
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10 0 0 10 400.5354 453.2598 cm
BT
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1 TL
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(120)Tj
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(10)Tj
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(43)Tj
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(2.4)Tj
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[()14( )13()]TJ
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(Rh02621745_g1\))Tj
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1 j
1 J
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1 TL
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0 -1.4976 Td
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(counts)Tj
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Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 272.1259 cm
BT
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1 TL
-0.004 Tc
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3.5489 0 Td
(lymphocyte)Tj
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(and)Tj
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(platelet)Tj
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(9)Tj
0.6917 0 Td
(post-irradiation)Tj
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(0.05\),)Tj
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(see)Tj
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1.4287 0 Td
(Fig)Tj
1.4797 0 Td
(1B)Tj
1.2755 0 Td
(and)Tj
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(1C)Tj
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(line)Tj
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(within)Tj
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(24)Tj
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1.8198 0 Td
(1D)Tj
0 g
(\),)Tj
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(a)Tj
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(3-fold)Tj
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(mean)Tj
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(increase)Tj
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(by)Tj
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(day)Tj
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(66,)Tj
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(\(p-value)Tj
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0 Tc
3.5149 0 Td
(<)Tj
/F7 1 Tf
-0.004 Tc
0.9921 0 Td
(0.05)Tj
1.8709 0 Td
(for)Tj
1.3833 0 Td
(both\),)Tj
2.6305 0 Td
(and)Tj
1.7291 0 Td
(corre-)Tj
-32.8646 -1.2983 Td
(sponding)Tj
3.9628 0 Td
(to)Tj
1.0261 0 Td
(the)Tj
1.4683 0 Td
(expected)Tj
3.7191 0 Td
(pattern)Tj
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(of)Tj
1.0148 0 Td
(radiation-induced)Tj
7.4721 0 Td
(pneumonitis.)Tj
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(third)Tj
2.211 0 Td
(significant)Tj
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1.0147 0 Td
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0.9524 0 Td
(185)Tj
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(days)Tj
2.0013 0 Td
(post-exposure,)Tj
6.0717 0 Td
(disappearing)Tj
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(by)Tj
1.1792 0 Td
(the)Tj
1.4683 0 Td
(study's)Tj
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(end)Tj
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(at)Tj
0.9524 0 Td
(day)Tj
1.6328 0 Td
(250.)Tj
-35.9147 -1.3039 Td
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3.5773 0 Td
(that)Tj
1.7801 0 Td
(were)Tj
2.1203 0 Td
(euthanized)Tj
4.6148 0 Td
(later)Tj
1.9899 0 Td
(for)Tj
1.3889 0 Td
(elevated)Tj
3.4526 0 Td
(respiratory)Tj
4.5978 0 Td
(rates)Tj
2.1033 0 Td
(had)Tj
1.7121 0 Td
(higher)Tj
2.8006 0 Td
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