Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Medical Oncology
Published in: Medical Oncology 2/2010

01-06-2010 | Original Paper

Twilight effects of low doses of ionizing radiation on cellular systems: a bird’s eye view on current concepts and research

Authors: Ilaria Postiglione, Angela Chiaviello, Giuseppe Palumbo

Published in: Medical Oncology | Issue 2/2010

Login to get access

Abstract

The debate about the health risks from low doses of radiation is vigorous and often acrimonious since many years and does not appear to weaken. Being far from completeness, this review presents only a bird’s eye view on current concepts and research in the field. It is organized and divided in two parts. The first is dedicated to molecular responses determined by radiation-induced DNA ruptures. It focuses its attention on molecular pathways that are activated by ATM and tries to describe the variegated functions and specific roles of Chk2 and p53 and other proteins in sensing, promoting and executing DNA repair. The second part is more concerned with the risk associated with exposure to low dose radiation and possible effects that the radiation-affected cell may undergo. These effects include induction of apoptosis and mitotic catastrophe, bystander effect and genomic instability, senescence and hormetic response. Current hypotheses and research on these issues are briefly discussed.
Literature
1.
Grubbé EH. Priority in the therapeutic use of X-rays. Radiology. 1933;21:156–62.
2.
Albers-Schonberg H. Uber line bischer unbekannte Wirkukng der Rontgenstnrahlen auf den organismus der tiere. Munch Med Wochenschr. 1903;50:1859–60.
3.
Heineke H. Ueber die Einwirkung der Röntgenstrahlen auf Tiere. Munch Med Wochenschr. 1903;50:2090–2.
4.
5.
Martland HS, Humphries RE. Osteogenic sarcoma in dial painters using luminous paint. Arch Pathol Lab Med. 1929;7:406–17.
6.
7.
8.
9.
10.
11.
12.
13.
14.
Haimovitz-Friedman A, Khan C, Ehleiter D, Persaud RS, McLoughlin M, Fuks Z, et al. Ionizing radiation acts on cellular membranes in human leukemia cells to generate ceramide and induce apoptosis. J Exp Med. 1994;180:525–35. doi:10.​1084/​jem.​180.​2.​525.PubMedCrossRef
15.
Michael JM, Lavin MF, Watters DJ. Resistance to radiation-induced apoptosis in Burkitt’s lymphoma cells is associated with defective ceramide signaling. Cancer Res. 1997;57:3600–5.PubMed
16.
17.
Bartek J, Falck J, Lukas J. CHK2 kinase—a busy messenger. Nat Rev Mol Cell Biol. 2001;2:877–86.PubMedCrossRef
18.
19.
20.
Andegeko Y, Moyal L, Mittelman L, Tsarfaty I, Shiloh Y, Rotman G. Nuclear retention of ATM at sites of DNA double strand breaks. J Biol Chem. 2001;276:38224–30.PubMed
21.
22.
23.
24.
Li S, Ting NS, Zheng L, Chen PL, Ziv Y, Shiloh Y, et al. Functional link of BRCA1 and ataxia telangiectasia gene product in DNA damage response. Nature. 2000;406:210–5. doi:10.​1038/​35018134.PubMedCrossRef
25.
Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER III, Hurov KE, Luo J, et al. ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science. 2007;316:1138–9. doi:10.​1126/​science.​1140321.CrossRef
26.
27.
28.
29.
Dalal SN, Schweitzer CM, Gan J, DeCaprio JA. Cytoplasmic localization of human cdc25C during interphase requires an intact 14-3-3 binding site. Mol Cell Biol. 1999;19:4465–79.PubMed
30.
Hall PA, Kearsey JM, Coates PJ, Norman DG, Warbrick E, Cox LS. Characterisation of the interaction between PCNA and Gadd45. Oncogene. 1995;10:2427–33.PubMed
31.
Smith ML, Chen IT, Zhan Q, Bae I, Chen CY, Gilmer TM, et al. Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen. Science. 1994;266:1376–80.PubMedCrossRef
32.
Chen IT, Akamatsu M, Smith ML, Lung FD, Duba D, Roller PP, et al. Characterization of p21Cip1/Waf1 peptide domains required for cyclin E/Cdk2 and PCNA interaction. Oncogene. 1996;12:595–607.PubMed
33.
34.
35.
36.
37.
38.
39.
40.
Dalal SN, Yaffe MB, DeCaprio JA. 14-3-3 family members act coordinately to regulate mitotic progression. Cell Cycle. 2004;3:672–7.PubMed
41.
42.
43.
44.
45.
46.
47.
Chen IT, Smith ML, O’Connor PM, Fornace AJ. Direct interaction of Gadd45 with PCNA and evidence for competitive interaction of Gadd45 and p21Waf1/Cip1 with PCNA. Oncogene. 1995;11:1931–7.PubMed
48.
49.
50.
51.
Jaberaboansari A, Nelson GB, Roti Roti JL, Wheeler KT. Post-irradiation alterations of neuronal chromatin structure. Radiat Res. 1998;114:94–104. doi:10.​2307/​3577147.CrossRef
52.
Malyapa RS, Wright WD, Taylor YC, Roti Roti JL. DNA supercoiling changes and nuclear matrix-associated proteins: possible role in oncogene-mediated radioresistance. Int J Radiat Oncol Biol Phys. 1996;35:963–73. doi:10.​1016/​0360-3016(96)00211-8.PubMed
53.
54.
55.
Iijima K, Ohara M, Seki R, Tauchi H. Dancing on damaged chromatin: functions of ATM and the RAD50/MRE11/NBS1 complex in cellular responses to DNA damage. J Radiat Res (Tokyo). 2008;49:451–64. doi:10.​1269/​jrr.​08065.CrossRef
56.
Celeste A, Fernandez-Capetillo O, Kruhlak MJ, Pilch DR, Staudt DW, Lee A, et al. Histone H2AX phosphorylation is dispensable for the initial recognition of DNA breaks. Nat Cell Biol. 2003;5:675–9. doi:10.​1038/​ncb1004.PubMedCrossRef
57.
58.
59.
60.
61.
62.
63.
64.
65.
66.
Bassing CH, Chua KF, Sekiguchi J, Suh H, Whitlow SR, Fleming JC, et al. Increased ionizing radiation sensitivity and genomic instability in the absence of histone H2AX. Proc Natl Acad Sci USA. 2002;99:8173–8. doi:10.​1073/​pnas.​122228699.PubMedCrossRef
67.
68.
69.
Carney JP, Maser RS, Olivares H, Davis EM, Le Beau M, Yater JR, et al. The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response. Cell. 1998;93:477–86. doi:10.​1016/​S0092-8674(00)81175-7.PubMedCrossRef
70.
71.
72.
73.
Snouwaert JN, Gowen LC, Latour AM, Mohn AR, Xiao A, DiBiase L, et al. BRCA1 deficient embryonic stem cells display a decreased homologous recombination frequency and an increased frequency of non-homologous recombination that is corrected by expression of a Brca1 transgene. Oncogene. 1999;18:7900–7. doi:10.​1038/​sj.​onc.​1203334.PubMedCrossRef
74.
75.
Barlow C, Liyanage M, Moens PB, Tarsounas M, Nagashima K, Brown K, et al. Atm deficiency results in severe meiotic disruption as early as leptonema of prophase I. Development. 1998;125:4007–17.PubMed
76.
Takata M, Sasaki MS, Sonoda E, Morrison C, Hashimoto M, Utsumi H, et al. Homologous recombination and non-homologous end-joining pathways of DNA double-strand break repair have overlapping roles in the maintenance of chromosomal integrity in vertebrate cells. EMBO J. 1998;17:5497–500. doi:10.​1093/​emboj/​17.​18.​5497.PubMedCrossRef
77.
78.
79.
Pierce DA, Shimizu Y, Preston DL, Vaeth M, Mabuchi K. Studies of the mortality of atomic bomb survivors. Report 12, Part I. Cancer: 1950–1990. Radiat Res. 1996;146:1–27. doi:10.​2307/​3579391.PubMedCrossRef
80.
81.
Preston DL, Kusumi S, Tomonaga M, et al. Cancer incidence in atomic bomb survivors. Part III. Leukemia, lymphoma and multiple myeloma, 1950–1987. Radiat Res. 1994;137:S68–97. doi:10.​2307/​3578893.PubMedCrossRef
82.
83.
Schull WJ. Radioepidemiology of the A-bomb survivors. Health Phys. 1996;70:798–803.PubMed
84.
85.
United Nations. Sources and effects of ionizing radiation. UNSCEAR 2000 report to the general assembly with scientific annexes. Volume II: Effects. Annex I, Epidemiological evaluation of radiation induced cancer. New York: United Nations, 2000.
86.
87.
Pollycove M. Low dose linearity: the rule or the exception. BELLE Newsl. 1997;6:13–8.
88.
National Council on Radiation Protection. Limitation of exposure to ionizing radiation: report 116. Bethesda, MD: National Council on Radiation Protection; 1993.
89.
International Commission on Radiological Protection. Recommendations of the International Commission on Radiological Protection. Ottawa: ICRP Publication; 1990.
90.
Scott BR, Di Palma J. Sparsely ionizing diagnostic and background radiations are likely preventing cancer and other genomic-instability-associated diseases. Dose Response. 2006;5:230–55.PubMedCrossRef
91.
92.
93.
United Nations. Sources and effects of ionizing radiation. UNSCEAR 2000 Report to the General Assembly with scientific annexes. Volume II: effects. Annex G, Biological effects at low radiation doses. 2000; New York: United Nations.
94.
Becker K. Threshold or no threshold, that is the question. Radiat Prot Dosim. 1997;71:3–5.
95.
96.
97.
Health Physics Society. Radiation risk in perspective: position statement of the Health Physics Society. In: Health Physics Society Directory and handbook, 1998–1999. McLean, VA: Health Physics Society; 1998. p. 238–244.
98.
Cai L, Liu SZ. Induction of cytogenetic adaptive response of somatic and germ cells in vivo and in vitro by low-dose X-irradiation. Int J Radiat Biol. 1990;58:187–94.PubMedCrossRef
99.
100.
101.
Shadley JD, Afzal V, Wolff S. Characterization of the adaptive response to ionizing radiationinduced by low doses of x-rays to human lymphocytes. Radiat Res. 1987;111:511–7. doi:10.​2307/​3576936.PubMedCrossRef
102.
103.
Hooker AM, Bhat M, Day TK, Lane JM, Swinburne SJ, Morley AA, et al. The linear nothreshold model does not hold for low-dose ionizing radiation. Radiat Res. 2004;162:447–52. doi:10.​1667/​RR3228.PubMedCrossRef
104.
Scott BR. Low-dose radiation risk extrapolation fallacy associated with the linear-no-threshold model. BELLE Newsl. 2005;13:22–7.
105.
Wang GJ, Li X-K, Sakai K, Cai L. Low-dose radiation and its clinical implications: diabetes. BELLE Newsl. 2005;13:12–21.
106.
Pollycove M, Feinendegen LE. Biologic response to low doses of ionizing radiation: detriment versus hormesis. Part 2. Dose responses of organisms. J Nucl Med. 2001;42:26N–37N.PubMed
107.
108.
Cohen BL. Cancer risk from low-level radiation. Am J Roentgenol. 2002;179:1137–43.
109.
110.
111.
Mitchel RE, Jackson JS, McCann RA, Boreham DR. The adaptive response modifies latency for radiation-induced myeloid leukemia in CBA/H mice. Radiat Res. 1999;152:273–9. doi:10.​2307/​3580327.PubMedCrossRef
112.
113.
114.
115.
116.
117.
Nagasawa H, Little JB. Induction of sister chromatid exchanges by extremely low doses of alpha-particles. Cancer Res. 1992;52:6394–6.PubMed
118.
Deshpande A, Goodwin EH, Bailey SM, Marrone BL, Lehnert BE. Alpha-particle-induced sister chromatid exchange in normal human lung fibroblasts: evidence for an extra-nuclear target. Radiat Res. 1996;145:260–7. doi:10.​2307/​3578980.PubMedCrossRef
119.
Azzam EI, de Toledo SM, Little JB. Direct evidence for the participation of gap junction-mediated intercellular communication in the transmission of damage signals from alpha-particle irradiated to non irradiated cells. Proc Natl Acad Sci USA. 2001;98:473–8. doi:10.​1073/​pnas.​011417098.PubMedCrossRef
120.
121.
122.
Mothersill C, Seymour CB. Cell–cell contact during gamma irradiation is not required to induce a bystander effect in normal human keratinocytes: evidence for release during irradiation of a signal controlling survival into the medium. Radiat Res. 1998;149:256–62. doi:10.​2307/​3579958.PubMedCrossRef
123.
124.
125.
126.
Shao C, Furusawa Y, Aoki M, Ando K. Role of gap junctional intercellular communication in radiation-induced bystander effects in human fibroblasts. Radiat Res. 2003;160:318–23. doi:10.​1667/​RR3044.PubMedCrossRef
127.
128.
Hamada N, Matsumoto H, Hara T, Kobayashi Y. Intercellular and intracellular signaling pathways mediating ionizing radiation-induced bystander effects. J Radiat Res (Tokyo). 2007;48:87–95. doi:10.​1269/​jrr.​06084.CrossRef
129.
Bourguignon MH, Gisone PA, Perez MR, Michelin S, Dubner D, Giorgio MD, et al. Genetic and epigenetic features in radiation sensitivity Part I: cell signalling in radiation response. Eur J Nucl Med Mol Imaging. 2005;32:229–46. doi:10.​1007/​s00259-004-1730-7. Review.PubMedCrossRef
130.
Huang L, Snyder AR, Morgan WF. Radiation-induced genomic instability and its implications for radiation carcinogenesis. Oncogene. 2003;22:5854–948.
131.
132.
Hamada N, Funayama T, Wada S, Sakashita T, Kakizaki T, Ni M, et al. LET-dependent survival of irradiated normal human fibroblasts and their descendents. Radiat Res. 2006;166:24–30. doi:10.​1667/​RR3579.​1.PubMedCrossRef
133.
Limoli CL, Giedzinski E, Morgan WF, Swarts SG, Jones GD, Hyun W. Persistent oxidative stress in chromosomally unstable cells. Cancer Res. 2003;63:3107–11.PubMed
134.
135.
136.
Moore SR, Marsden S, Macdonald D, Mitchell S, Folkard M, Michael B, et al. Genomic instability in human lymphocytes irradiated with individual charged particles: involvement of tumor necrosis factor alpha in irradiated cells but not bystander cells. Radiat Res. 2005;163:183–90. doi:10.​1667/​RR3298.PubMedCrossRef
137.
138.
139.
140.
141.
Aldridge DR, Radford IR. Explaining differences in sensitivity to killing by ionizing radiation between human lymphoid cell lines. Cancer Res. 1998;58:2817–24.PubMed
142.
143.
144.
145.
Bracey TS, Miller JC, Paraskeva C. Radiation induced apoptosis in human colorectal adenoma and carcinoma cell lines can occur in the absence of wild type p53. Oncogene. 1995;10:2391–6.PubMed
146.
Guillouf C, Rosselli F, Sjin RT, Moustacchi E, Hofman B, Liebermann DA. Role of a mutant p53 protein in apoptosis: characterization of a function independent of transcriptional trans-activation. Int J Oncol. 1998;13:107–14.PubMed
147.
Merritt A, Allen TD, Potten CS, Hickman JA. Apoptois in small intestinal epithelia from p53-null mice: evidence for a delayed, p53-independent G2/M-associated cell death after g-irradiation. Oncogene. 1997;14:2759–66. doi:10.​1038/​sj.​onc.​1201126.PubMedCrossRef
148.
Castedo M, Perfettini JL, Roumierh T, Valent A, Raslova H, Yakushijin K, et al. Mitotic catastrophe constitutes a special case of apoptosis whose suppression entails aneuploidy. Oncogene. 2004;23:4362–70. doi:10.​1038/​sj.​onc.​1207572.PubMedCrossRef
149.
Eriksson D, Lofroth PO, Johansson L, Riklund KA, Stigbrand T. Cell cycle disturbances and mitotic catastrophes in HeLa Hep2 cells following 2.5 to 10 Gy of ionizing radiation. Clin Cancer Res. 2007;13:5501–8.CrossRef
150.
151.
Ianzini F, Bertoldo A, Kosmacek EA, Phillips SL, Mackey MA. Lack of p53 function promotes radiation-induced mitotic catastrophe in mouse embryonic fibroblast cells. Cancer Cell Int. 2006;6:11–8. doi:10.​1186/​1475-2867-6-11.PubMedCrossRef
152.
Luce A, Courtin A, Levalois C, Altmeyer-Morel S, Romeo PH, Chevillard S, et al. Death receptor pathways mediate targeted and non-targeted effects of ionizing radiations in breast cancer cells. Carcinogenesis. 2009;30:432–9. doi:10.​1093/​carcin/​bgp008.PubMedCrossRef
153.
154.
Campisi J. Cellular senescence as a tumour-suppressor mechanism. Trends Cell Biol. 2001;11:27–31.
155.
156.
157.
158.
159.
Chu K, Teele N, Dewey MW, Albright N, Dewey WC. Computerized video time lapse study of cell cycle delay and arrest, mitotic catastrophe, apoptosis and clonogenic survival in irradiated 14–3-3sigma and CDKN1A (p21) knockout cell lines. Radiat Res. 2004;162:270–86. doi:10.​1667/​RR3221.PubMedCrossRef
160.
Mirzayans R, Scott A, Cameron M, Murray D. Induction of accelerated senescence by gamma radiation in human solid tumour-derived cell lines expressing wild-type TP53. Radiat Res. 2005;163:53–62. doi:10.​1667/​RR3280.PubMedCrossRef
161.
Chang BD, Xuan Y, Broude EV, Zhu H, Schott B, Fang J, et al. Role of p53 and p21waf1/cip1 in senescence-like terminal proliferation arrest induced in human tumor cells by chemotherapeutic drugs. Oncogene. 1999;18:4808–18. doi:10.​1038/​sj.​onc.​1203078.PubMedCrossRef
162.
Podtcheko A, Ohtsuru A, Namba H, Saenko V, Starenki D, Palona I, et al. Inhibition of ABL tyrosine kinase potentiates radiation-induced terminal growth arrest in anaplastic thyroid cancer cells. Radiat Res. 2006;165:35–42. doi:10.​1667/​RR3466.​1.PubMedCrossRef
163.
Lehman BD, McCubrey JA, Jeffrerson HS, Paine MS, Chappel WH, Terrian DM. A dominant role for p53 dependent cellular senescence in radiosensitization of human prostate cancer cells. Cell Cycle. 2007;6:595–605.
Metadata
Title
Twilight effects of low doses of ionizing radiation on cellular systems: a bird’s eye view on current concepts and research
Authors
Ilaria Postiglione
Angela Chiaviello
Giuseppe Palumbo
Publication date
01-06-2010
Publisher
Springer US
Published in
Medical Oncology / Issue 2/2010
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-009-9241-9

Other articles of this Issue 2/2010

Medical Oncology 2/2010 Go to the issue

Original Paper

Polymorphisms of TP53 codon 72 with prostate carcinoma risk: a meta-analysis

Original Paper

Utility of DNA postreplication repair protein Rad6B in neoadjuvant chemotherapy response

Original Paper

Sarcomatoid carcinoma of the urinary bladder: a case report with immunohistochemical and molecular genetic analysis

Original Paper

Anticancer effect of realgar nanoparticles on mouse melanoma skin cancer in vivo via transdermal drug delivery

Original Paper

Olecranon bursitis in patients treated with sunitinib for renal cell carcinoma

Original Paper

Immunohistochemical detection of the Raf kinase inhibitor protein in nonneoplastic gastric tissue and gastric cancer tissue
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits