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Radiation-induced Versus Endogenous DNA Damage: Possible Effect Of Inducible Protective Responses In Mitigating Endogenous Damage

M. Pollycove, L. Feinendegen
Published 2003 · Biology, Medicine

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Ionizing radiation (IR) causes damage to DNA that is apparently proportional to absorbed dose. The incidence of radiation-induced cancer in humans unequivocally rises with the value of absorbed doses above about 300 mGy, in a seemingly linear fashion. Extrapolation of this linear correlation down to zero-dose constitutes the linear-no-threshold (LNT) hypothesis of radiation-induced cancer incidence. The corresponding dose-risk correlation, however, is questionable at doses lower than 300 mGy. Non-radiation induced DNA damage and, in consequence, oncogenic transformation in non-irradiated cells arises from a variety of sources, mainly from weak endogenous carcinogens such as reactive oxygen species (ROS) as well as from micronutrient deficiencies and environmental toxins. In order to relate the low probability of radiation-induced cancer to the relatively high incidence of non-radiation carcinogenesis, especially at low-dose irradiation, the quantitative and qualitative differences between the DNA damages from non-radiation and radiation sources need to be addressed and put into context of physiological mechanisms of cellular protection. This paper summarizes a co-operative approach by the authors to answer the questions on the quantitative and qualitative DNA damages from non-radiation sources, largely endogenous ROS, and following exposure to low doses of IR. The analysis relies on published data and justified assumptions and considers the physiological capacity of mammalian cells to protect themselves constantly by preventing and repairing DNA damage. Furthermore, damaged cells are susceptible to removal by apoptosis or the immune system. The results suggest that the various forms of non-radiation DNA damage in tissues far outweigh corresponding DNA damage from low-dose radiation exposure at the level of, and well above, background radiation. These data are examined within the context of low-dose radiation induction of cellular signaling that may stimulate cellular protection systems over hours to weeks against accumulation of DNA damage. The particular focus is the hypothesis that these enhanced and persisting protective responses reduce the steady state level of nonradiation DNA damage, thereby reducing deleterious outcomes such as cancer and aging. The emerging model urgently needs rigorous experimental testing, since it suggests, importantly, that the LNT hypothesis is invalid for complex adaptive systems such as mammalian organisms.
This paper references
Induction of the adaptive response by X - rays is dependent on radiation intensity
JD Shadley (1989)
10.1007/BF01209749
The quality of DNA double-strand breaks: A Monte Carlo simulation of the end-structure of strand breaks produced by protons and alpha particles
A. Ottolenghi (1995)
Biological effects of low level exposures to chemicals and radiation
E. Calabrese (1992)
10.1080/01635589209514201
Fruit, vegetables, and cancer prevention: a review of the epidemiological evidence.
G. Block (1992)
10.1097/00004032-199007000-00003
T cell potentiation by low dose ionizing radiation: possible mechanisms.
T. Makinodan (1990)
10.1016/S0304-4165(98)00043-9
Induction of mRNAs for glutathione synthesis-related proteins in mouse liver by low doses of gamma-rays.
S. Kojima (1998)
10.1093/CARCIN/19.7.1163
Folate, vitamin B12, homocysteine status and DNA damage in young Australian adults.
M. Fenech (1998)
Indian research on high levels of natural radiation : pertinent observations for further studies
PC Kesavan
10.2307/3579865
Intercellular communication is involved in the bystander regulation of gene expression in human cells exposed to very low fluences of alpha particles.
E. Azzam (1998)
CELLULAR AND SUBCELLULAR EFFECTS OF IONIZING RADIATIONS.
P. Montgomery (1964)
Positive health effects of low level radiation in human populations
M Pollycove
10.1016/S0027-5107(96)00118-2
Hypersensitivity to very-low single radiation doses: its relationship to the adaptive response and induced radioresistance.
M. Joiner (1996)
10.1080/09553008814550391
Biochemical and cellular mechanisms of low-dose effects.
L. Feinendegen (1988)
10.1080/09553008814550401
Human lymphocytes exposed to low doses of ionizing radiations become refractory to high doses of radiation as well as to chemical mutagens that induce double-strand breaks in DNA.
S. Wolff (1988)
Recent radiological studies of high - level natural radiation areas of Ramsar
M Sohrabi (1990)
10.1139/O96-089
The importance of the microenvironment in breast cancer progression: recapitulation of mammary tumorigenesis using a unique human mammary epithelial cell model and a three-dimensional culture assay.
V. Weaver (1996)
10.1016/B978-0-12-035409-2.50009-6
Radiation-Induced Strand Breaks in DNA: Chemical and Enzymatic Analysis of End Groups and Mechanistic Aspects
C. Sonntag (1981)
10.1073/PNAS.92.12.5258
The causes and prevention of cancer.
B. Ames (1995)
10.1126/SCIENCE.1056154
Human DNA Repair Genes
R. Wood (2001)
10.1038/35041687
Oxidants, oxidative stress and the biology of ageing
T. Finkel (2000)
10.1016/0304-3835(95)03980-B
Improved genomic/nuclear DNA extraction for 8-hydroxydeoxyguanosine analysis of small amounts of rat liver tissue.
D. Nakae (1995)
Multifactorial analysis of lung cancer dose - response relationships for workers at the Mayak Nuclear Enterprise
ZB Tokarskaya (1997)
10.1056/NEJM198911093211902
Mortality from breast cancer after irradiation during fluoroscopic examinations in patients being treated for tuberculosis.
A. Miller (1989)
10.1097/00004032-199502000-00002
Test of the linear-no threshold theory of radiation carcinogenesis for inhaled radon decay products.
B. Cohen (1995)
10.1016/S0027-5107(96)00120-0
Radioadaptive response: efficient repair of radiation-induced DNA damage in adapted cells.
T. Ikushima (1996)
10.1080/18811248.1999.9726174
I. Evidence That There are Threshold Effects in Risk of Radiation
S. Kondo (1999)
10.2307/3579792
Induction of an adaptive response against spontaneous neoplastic transformation in vitro by low-dose gamma radiation.
J. Redpath (1998)
Alpha particles initiate biological production of superoxide anions and hydrogen peroxide in human cells.
P. Narayanan (1997)
10.1093/CARCIN/17.4.787
Determination of 8-hydroxydeoxyguanosine in human cells under oxygen-free conditions.
M. Nakajima (1996)
10.1016/S0764-4469(99)80051-1
Cellular signal adaptation with damage control at low doses versus the predominance of DNA damage at high doses.
L. Feinendegen (1999)
10.1016/0921-8777(94)00061-A
DNA repair comes of age.
P. Hanawalt (1995)
10.1038/NM0596-577
p53-dependent apoptosis suppresses radiation–induced teratogenesis
T. Norimura (1996)
10.1021/TX00030A013
Nickel(II)-mediated oxidative DNA base damage in renal and hepatic chromatin of pregnant rats and their fetuses. Possible relevance to carcinogenesis.
K. Kasprzak (1992)
10.1111/j.1749-6632.2000.tb06655.x
Biogerontology: The Next Step
S. Rattan (2000)
Induction of sister chromatid exchanges by extremely low doses of alpha-particles.
H. Nagasawa (1992)
10.2307/3579809
Enzymatic processing of radiation-induced free radical damage in DNA.
S. Wallace (1998)
10.1073/PNAS.97.2.686
A method for detecting abasic sites in living cells: age-dependent changes in base excision repair.
H. Atamna (2000)
10.1098/RSTB.1996.0139
The Croonian Lecture, 1996: endogenous damage to DNA.
T. Lindahl (1996)
10.1073/PNAS.95.9.5061
Activation of apurinic/apyrimidinic endonuclease in human cells by reactive oxygen species and its correlation with their adaptive response to genotoxicity of free radicals.
C. V. Ramana (1998)
10.11182/JASTRO1989.9.161
FUNDAMENTAL AND CLINICAL STUDIES ON CANCER CONTROL WITH TOTAL OR UPPER HALF BODY IRRADIATION
Kiyohiko Sakamoto (1997)
10.1016/S0921-8777(01)00063-5
The major human abasic endonuclease: formation, consequences and repair of abasic lesions in DNA.
D. Wilson (2001)
Induction of Sister Chromatid Exchanges by Extremely Low Doses of α-Particles
H. Nagasawa (1992)
10.2307/3580134
Population study in the high natural background radiation area in Kerala, India.
M. Nair (1999)
10.1006/JMBI.1995.0348
The action of Escherichia coli endonuclease III on multiply damaged sites in DNA.
M. A. Chaudhry (1995)
10.1111/J.1539-6924.1998.TB01287.X
Test of the Linear‐No Threshold Theory
B. Cohen (1998)
Cellular mechanisms of protection and repair induced by radiation exposure and their consequences for cell system responses.
L. Feinendegen (1995)
10.1080/09553009314550221
Does the enzymatic conversion of DNA single-strand damage into double-strand breaks contribute to biological inactivation of gamma-irradiated plasmid DNA?
Y. Ventur (1993)
10.2307/3580056
On the complexity of the DNA damage created by endogenous processes.
R. Stewart (1999)
10.1016/S0378-4274(98)00269-0
Micronutrients prevent cancer and delay aging.
B. Ames (1998)
10.1073/PNAS.94.7.3290
Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: implications for cancer and neuronal damage.
B. C. Blount (1997)
10.1016/S0921-8777(99)00050-6
A phylogenomic study of DNA repair genes, proteins, and processes.
J. Eisen (1999)
10.1080/09553009514551261
Role of molecular biology in radiation biology.
P. H. Lohman (1995)
10.1038/269518a0
Extreme sensitivity of some intestinal crypt cells to X and γ irradiation
CHRISTOPHER S. Potten (1977)
10.2307/3580135
Genetic monitoring of the human population from high-level natural radiation areas of Kerala on the southwest coast of India. I. Prevalence of congenital malformations in newborns.
G. Jaikrishan (1999)
10.1097/00004032-198705000-00020
Intracellular stimulation of biochemical control mechanisms by low-dose, low-LET irradiation.
L. Feinendegen (1987)
10.1097/00004032-200201000-00011
VERY HIGH BACKGROUND RADIATION AREAS OF RAMSAR, IRAN: PRELIMINARY BIOLOGICAL STUDIES
M. Ghiassi-nejad (2002)
10.1080/09553009014551461
Modification of effects of radiation on thymidine kinase.
K. Hohn-Elkarim (1990)
10.1038/35041694
The age of cancer
R. DePinho (2000)
10.1126/SCIENCE.280.5366.1066
Inducible repair of thymine glycol detected by an ultrasensitive assay for DNA damage.
X. Le (1998)
10.1016/0921-8777(94)90029-9
Biological inactivation of pBR322 plasmid DNA by enzyme- and radiation-induced single-strand damage under various conditions.
Y. Ventur (1994)
10.1667/0033-7587(2000)153[0508:RCOBAT]2.0.CO;2
Relative Contribution of Bystander and Targeted Cell Killing to the Low-Dose Region of the Radiation Dose–Response Curve
C. Seymour (2000)
10.1080/09553008914551231
Induction of the adaptive response by X-rays is dependent on radiation intensity.
J. Shadley (1989)
10.1016/0304-3835(96)04320-0
DNA base damage in lymphocytes of cancer patients undergoing radiation therapy.
R. Olinski (1996)
10.1016/S0891-5849(00)00302-6
Triggering and modulation of apoptosis by oxidative stress.
J. Chandra (2000)
10.1152/PHYSREV.1979.59.3.527
Hydroperoxide metabolism in mammalian organs.
B. Chance (1979)
10.1093/NAR/24.8.1389
Repair of products of oxidative DNA base damage in human cells.
P. Jaruga (1996)
10.1007/BF00265430
Survival of phage M13 with uracils on one or both DNA strands
S. Schünemann (2004)
10.1667/0033-7587(2001)156[0177:ARATBE]2.0.CO;2
Adaptive Response and the Bystander Effect Induced by Radiation in C3H 10T½ Cells in Culture
S. Sawant (2001)
10.1016/0891-5849(91)90127-O
Increased SOD activities and decreased lipid peroxide levels induced by low dose X irradiation in rat organs.
K. Yamaoka (1991)
10.2307/3576760
Mammalian cells are not killed by DNA single-strand breaks caused by hydroxyl radicals from hydrogen peroxide.
J. Ward (1985)
10.1667/0033-7587(2001)156[0618:ESTTMA]2.0.CO;2
Extracellular Signaling through the Microenvironment: A Hypothesis Relating Carcinogenesis, Bystander Effects, and Genomic Instability
M. Barcellos-Hoff (2001)
The quanti Ž cation of physical events within tissue at low levels of exposure to ionizing radiation
LE Feinendegen (1979)
10.1097/00004032-199712000-00003
Multifactorial analysis of lung cancer dose-response relationships for workers at the Mayak nuclear enterprise.
Z. B. Tokarskaya (1997)
10.2172/10103020
Health effects of low-level radiation in shipyard workers
Matanoski (1984)
10.1038/35041682
Why do we age?
T. Kirkwood (2000)
10.1016/S1383-5742(99)00056-3
Micronucleus frequency in human lymphocytes is related to plasma vitamin B12 and homocysteine.
M. Fenech (1999)
10.1016/S0027-5107(96)00121-2
Radiation effects induced by low doses in complex tissue and their relation to cellular adaptive responses.
L. Feinendegen (1996)
10.1073/PNAS.95.1.288
DNA oxidation matters: the HPLC-electrochemical detection assay of 8-oxo-deoxyguanosine and 8-oxo-guanine.
H. Helbock (1998)
10.1038/155210A0
Biphasic Action of Penicillin and other Sulphonamide Similarity
W. Miller (1945)
10.1016/S0027-5107(97)00070-5
'Spontaneous' genetic damage in man: evaluation of interindividual variability, relationship among markers of damage, and influence of nutritional status.
J. Macgregor (1997)
10.2307/3580136
Genetic monitoring of the human population from high-level natural radiation areas of Kerala on the southwest coast of India. II. Incidence of numerical and structural chromosomal aberrations in the lymphocytes of newborns.
V. D. Cheriyan (1999)
10.2307/3579298
Low-dose ionizing radiation decreases the frequency of neoplastic transformation to a level below the spontaneous rate in C3H 10T1/2 cells.
E. Azzam (1996)
Apoptosis : its roles and mechanism
山田 武 (1998)
10.1126/SCIENCE.289.5484.1567
Extension of life-span with superoxide dismutase/catalase mimetics.
S. Melov (2000)
10.1016/S0360-3016(98)80333-7
The suppression of metastases and the change in host immune response after low-dose total-body irradiation in tumor-bearing rats.
S. Hashimoto (1999)
10.1016/0048-9697(94)90080-9
Long-term irradiation effects in the population evacuated from the east-Urals radioactive trace area.
V. A. Kostyuchenko (1994)
Test of the linear no-threshold theory.
P. Price (1995)
Biological Effects of Low Level Exposures Dose-Response Relationships
E. Calabrese (1994)
10.1021/TX00039A009
Oxidative DNA base damage in renal, hepatic, and pulmonary chromatin of rats after intraperitoneal injection of cobalt(II) acetate.
K. Kasprzak (1994)
10.1289/EHP.98106S1363
Nonlinearity of radiation health effects.
M. Pollycove (1998)
10.1074/jbc.272.32.19633
Oxidative Decay of DNA*
K. B. Beckman (1997)
10.1038/218652A0
Defective Repair Replication of DNA in Xeroderma Pigmentosum
J. Cleaver (1968)
10.1152/PHYSREV.1998.78.2.547
The free radical theory of aging matures.
K. B. Beckman (1998)
10.1016/S0764-4469(99)80044-4
Molecular biology, epidemiology, and the demise of the linear no-threshold (LNT) hypothesis.
M. Pollycove (1999)
10.1148/103.1.46
Radiation Quantities and Units
Herbert M. Parker (1972)
10.1016/0891-5849(94)00171-F
DNA base modifications and antioxidant enzyme activities in human benign prostatic hyperplasia.
R. Olinski (1995)
10.2307/3579259
Clastogenic factors in the plasma of Chernobyl accident recovery workers: anticlastogenic effect of Ginkgo biloba extract.
I. Emerit (1995)
Cellular and Molecular Immunology
A. Abbas (1991)
10.1007/S004110050058
Radiogenic lung cancer: the effects of low doses of low linear energy transfer (LET) radiation
H. Rossi (1997)
10.1073/PNAS.90.4.1614
DNA repair and aging in basal cell carcinoma: a molecular epidemiology study.
Q. Wei (1993)
10.1080/09553008814550381
A microdosimetric understanding of low-dose radiation effects.
J. Booz (1988)
10.1016/S0764-4469(99)80040-7
Adaptive response and induced resistance.
M. Joiner (1999)
10.1016/S0079-6603(08)60611-X
DNA damage produced by ionizing radiation in mammalian cells: identities, mechanisms of formation, and reparability.
J. Ward (1988)
10.1007/BF01210408
Induction, repair and biological relevance of radiation-induced DNA lesions in eukaryotic cells
M. Frankenberg-Schwager (1990)
Nickel ( 11 ) - mediated oxidative DNA base damage in rat renal chromatin in vivo . Possible relevance to nickel ( II ) carcinogenesis
KS Kasprzak (2001)
The Quark and the Jaguar
J. A. Sutherland (1994)



This paper is referenced by
10.1259/BJR/63353075
Evidence for beneficial low level radiation effects and radiation hormesis.
L. Feinendegen (2005)
10.1016/J.ASR.2006.03.030
Adaptive hormetic response of pre-exposure of mouse brain with low-dose 12C6+ ion or 60Co γ-ray on growth hormone (GH) and body weight induced by subsequent high-dose irradiation
H. Zhang (2006)
10.1504/IJNKM.2004.005148
Why are we so afraid of nuclear radiation
J. Cuttler (2004)
10.1007/S00411-006-0073-0
Cytogenetic effects of low-dose radiation with different LET in human peripheral blood lymphocytes
E. Nasonova (2006)
10.1097/HP.0b013e31820a83ae
Biological consequences and health risks of low-level exposure to ionizing radiation: commentary on the workshop.
L. Feinendegen (2011)
Hormeza zjawisko powszechne i powszechnie nieznane
L. Dobrzynski (2006)
10.1177/1559325816640073
Treatment of Alzheimer Disease With CT Scans
J. Cuttler (2016)
10.1016/J.EJRAD.2007.09.028
The thyroid dose burden in medical imaging A re-examination.
P. Dawson (2009)
10.1080/09553002.2019.1606957
Study of mutation from DNA to biological evolution
Masako Bando (2019)
10.1007/978-3-642-55539-8_33
Biological Effects of Low Doses of Ionizing Radiation: Damage versus Protection
L. Feinendegen (2003)
10.1007/S00411-007-0146-8
Systems biology and its potential role in radiobiology
L. Feinendegen (2008)
10.2203/dose-response.13-055.Cuttler
Remedy for Radiation Fear — Discard the Politicized Science
Jerry R. Cuttler (2014)
Paper FIFTH WARREN K. SINCLAIR KEYNOTE ADDRESS: ISSUES IN QUANTIFYING THE EFFECTS OF LOW-LEVEL RADIATION
Dudley T. Goodhead (2009)
A REVIEW : DEVELOPMENT OF A MICRODOSE MODEL FOR ANALYSIS OF ADAPTIVE RESPONSE AND BYSTANDER DOSE RESPONSE BEHAVIOR
S. Park (2014)
10.1007/978-1-4020-6335-0_22
Radiation, Oxidative Stress and Senescence; The Vascular Endothelial Cell as a Common Target
P. Schofield (2007)
10.2203/dose-response.06-112.Pollycove
Radiobiological Basis of Low-Dose Irradiation in Prevention and Therapy of Cancer
M. Pollycove (2006)
10.1504/AFP.2007.015827
Damage propagation in complex biological systems following exposure to low doses of ionising radiation
L. Feinendegen (2007)
10.2203/dose-response.06-002.Scott
Sparsely Ionizing Diagnostic and Natural Background Radiations are Likely Preventing Cancer and other Genomic-Instability-Associated Diseases
B. Scott (2006)
10.1111/JFBC.12877
Hormesis effect of hydrogen peroxide on the promoter activity of neuropeptide receptor PAC1-R.
Xiaoling Huang (2019)
In Search for Biomarkers of Aging : A Proteomics Approach
R. Klooster (2006)
Novel treatment strategies for breast, lung and cervical cancer
Mogammad Baahith Hamid (2019)
10.1080/09553002.2020.1812760
Evaluation of induced biological effects in rats by continuous and natural gamma radiation using a physical simulator
J. V. S. Coutinho (2020)
10.1667/RR14575.1
Multiple CT Scans Extend Lifespan by Delaying Cancer Progression in Cancer-Prone Mice
J. Lemon (2017)
10.11106/CET.2015.8.1.1
Thyroid Cancer and Radiation
C. Kim (2015)
10.2203/dose-response.09-011.Monfared
Association between Local External Gamma Rays and Frequency of Cancer in Babol-Iran
A. Monfared (2010)
10.1177/1559325820921641
Death of the ALARA Radiation Protection Principle as Used in the Medical Sector
Paul A Oakley (2020)
10.1186/s41021-018-0108-1
Collaborative study of thresholds for mutagens: proposal of a typical protocol for detection of hormetic responses in cytotoxicity tests
Shizuyo Sutou (2018)
10.1097/HP.0000000000000833
Biological Effects From Low Doses and Dose Rates of Ionizing Radiation: Science in the Service of Protecting Humans, a Synopsis
L. Feinendegen (2018)
10.1177/0194599813496377
Reactive Oxygen Species in Chronic Rhinosinusitis and Secondhand Smoke Exposure
M. Fordham (2013)
10.1016/j.radonc.2009.04.005
Effects of genistein following fractionated lung irradiation in mice.
Andrea E Para (2009)
10.3390/ijms140815931
Mechanisms of Radiation Toxicity in Transformed and Non-Transformed Cells
Ronald-Allan M. Panganiban (2013)
10.1080/15583724.2019.1641515
Recent Progress in the Biological Applications of Reactive Oxygen Species-Responsive Polymers
Zhiyuan Fan (2020)
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