Radiobiologists have been struggling to estimate the health risks from low doses of radiation in humans for decades. Health risks involve not only neoplastic diseases but also somatic mutations that may contribute to other illnesses (including birth defects and ocular maladies) and heritable mutations that may increase the risk of diseases in future generations. Low dose radiation-induced cancer in humans depends on several variables, and most of these variables are not possible to correct for in any epidemiologic study. Some of the confounding factors include (i) interaction of radiation with other physical (UV light), chemical, and biological mutagens and carcinogens in a synergistic manner; (ii) variation in repair mechanisms that depend on dose; (iii) variation in sensitivity of bystander cells to subsequent radiation exposure that depends on whether they have been pre- or postirradiated; and (iv) variation in adaptive response that depends on radiation doses and protective substances (antioxidants). In our opinion, both the linear no-threshold-response and the threshold-response models might not be suitable in predicting cancer risk at low radiation doses in a quantitative sense. Low doses of ionizing radiation should not be considered insignificant for risks of somatic and heritable, mutations and neoplastic and nonneoplastic diseases in humans.
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, pp238–244, 1998.
2.
Anonymous. Biological Effects of Ionizing Radiation BEIR V. Washington, DC: National Academy Press, Committee on the Biological Effects of Ionizing Radiation, 1990.
3.
PrasadKN, HovlandAR, NahreiniP, ColeWC, HovlandP, KumarB, PrasadKC. Differentiation genes: are they primary targets for human carcinogenesis?Exp Biol Med226:805–813, 2001.
4.
Court-BrownW, DollR, Eds. Leukemia and Aplastic Anemia in Patients Irradiated for Ankylosing Spondylitis. London: Her Majesty's Stationery Office, 1957.
5.
National Council Radiation Protection Measurements. Recommendations on Limits for Exposure to Ionizing Radiation. Publication 91. Bethesda, MD: National Council on Radiation Protection & Measurements, 1987.
6.
SnowbyF.Annals of the ICRP. Publication 26. New York: Elsevier, pp1–53, 1977.
7.
BondVP, BenaryV, SondhausCA. A different perception of the linear, nonthreshold hypothesis for low-dose irradiation. Proc Natl Acad Sci U S A88:8666–8670, 1991.
8.
CohenBL. Cancer risk from low-level radiation. Am J Roentgenol179:1137–1143, 2002.
MakinodanT, JamesSJ. T cell potentiation by low dose ionizing radiation: possible mechanisms. Health Phys59:29–34, 1990.
11.
MakinodanT.Cellular and sub-cellular alteration in immune cells induced by chronic intermittent exposure in vivo to very low dose of ionizing radiation and its ameliorating effects on progression of autoimmune disease and mammary tumor growth. In: SugaharaT, SaganL, AoyamaT, Eds. Low Dose Irradiation and Biological Defense Mechanisms. Amsterdam: Elsevier Science, pp233–237, 1992.
12.
Fritz-NiggliH, Schaeppi-BuechiC.Adaptive response to dominant lethality of mature (class A) and immature (class B) oocytes of D. melanogaster to low doses of ionizing radiation: effects in repair-proficient (yw) and repair-deficient strains (mei 41D5 and mus 302D1). Int J Radiat Biol59:175–184, 1991.
13.
KelseyKT, MemisogluA, FrenkelD, LiberHL. Human lymphocytes exposed to low doses of X-rays are less susceptible to radiation-induced mutagenesis. Mutat Res263:197–201, 1991.
14.
YamaokaK, EdamatsuR, MoriA.Increased SOD activities and decreased lipid peroxide levels induced by low dose X irradiation in rat organs. Free Radic Biol Med11:299–306, 1991.
15.
AndersonR: Effects of low dose radiation on the immune response. In: CalabreseE, Ed. Biological Effects of Low Level Exposures to Chemicals and Radiation. Chelsea, MI: Lewis, pp95–112, 1992.
16.
LiuS.Multilevel mechanisms of stimulatory effect of low dose radiation on immunity. In: SuguharaT, SaganL, AoyamaT, Eds. Low Dose Irradiation and Biological Defense Mechanisms. Amsterdam: Elsevier Science, pp225–232, 1992.
17.
AzzamEI, de ToledoSM, RaaphorstGP, MitchelRE. Low-dose ionizing radiation decreases the frequency of neoplastic transformation to a level below the spontaneous rate in C3H 10T1/2 cells. Radiat Res146:369–373, 1996.
18.
SakamotoK, MyoginM, HosoiY, OgawaY, NemotoK, TakaiY, KakutoY, YamadaS, WatabenN.Fundamental and clinical studies on cancer control with total and upper half body irradiation. J Jpn Soc Ther Radiol Oncol9:161–175, 1997.
19.
LeXC, XingJZ, LeeJ, LeadonSA, WeinfeldM.Inducible repair of thymine glycol detected by an ultrasensitive assay for DNA damage (comment). Science280:1066–1069, 1998.
20.
RedpathJL, AntonionoRJ. Induction of an adaptive response against spontaneous neoplastic transformation in vitro by low-dose gamma radiation. Radiat Res149:517–520, 1998.
21.
HashimotoS, ShiratoH, HosokawaM, NishiokaT, KuramitsuY, MatushitaK, KobayashiM, MiyasakaK.The suppression of metastases and the change in host immune response after low-dose total-body irradiation in tumor-bearing rats. Radiat Res151:717–724, 1999.
22.
HoweGR. Lung cancer mortality between 1950 and 1987 after exposure to fractionated moderate-dose-rate ionizing radiation in the Canadian fluoroscopy cohort study and a comparison with lung cancer mortality in the Atomic Bomb survivors study. Radiat Res142:295–304, 1995.
HerskowitzI.Damage to offspring of irradiated women. Prog Immunol Gynecol3:374–379, 1957.
25.
NewcombeHB, McGregorJF. Childhood cancer following obstetric radiography. Lancet2:1151–1152, 1971.
26.
StewartA, KnealeGW. Radiation dose effects in relation to obstetric x-rays and childhood cancers. Lancet1:1185–1188, 1970.
27.
UchidaIA, HolungaR, LawlerC.Maternal radiation and chromosomal aberrations. Lancet2:1045–1049, 1968.
28.
MossmanKL. Deconstructing radiation hormesis (comment). Health Phys80:263–269, 2001.
29.
SmithH.Radiation hormesis in relation to radiation protection. Chin Med J107:615–623, 1994.
30.
MorganWF. Non-targeted and delayed effects of exposure to ionizing radiation: II. Radiation-induced genomic instability and bystander effects in vivo, clastogenic factors and transgenerational effects. Radiation Research159:581–596, 2003.
31.
HuangL, SnyderAR, MorganWF. Radiation-induced genomic instability and its implications for radiation carcinogenesis. Oncogene22:5848–5854, 2003.
32.
McIlrathJ, LorimoreSA, CoatesPJ, WrightEG. Radiation-induced genomic instability in immortalized haemopoietic stem cells. Int J Radiat Biol79:27–34, 2003.
33.
MothersillC, SeymourC.Low-dose radiation effects: experimental hematology and the changing paradigm. Exp Hematol31:437–445, 2003.
34.
MothersillC, CreanM, LyonsM, McSweeneyJ, MooneyR, O'ReillyJ, SeymourCB. Expression of delayed toxicity and lethal mutations in the progeny of human cells surviving exposure to radiation and other environmental mutagens. Int J Radiation Biol74:673–680, 1998.
35.
EvansHH, HorngMF, RicanatiM, Diaz-InsuaM, JordanR, SchwartzJL. Induction of genomic instability in TK6 human lymphoblasts exposed to 137Cs gamma radiation: comparison to the induction by exposure to accelerated 56Fe particles. Radiat Res159:737–747, 2003.
36.
LorimoreSA, WrightEG. Radiation-induced genomic instability and bystander effects: related inflammatory-type responses to radiation-induced stress and injury? A review. Int J Radiat Biol79:15–25, 2003.
37.
ZhouH, Randers-PehrsonG, WaldrenCA, VannaisD, HallEJ, HeiTK, ChatterjeeA.Induction of a bystander mutagenic effect of alpha particles in mammalian cells. Proc Natl Acad Sci U S A97:2099–2104, 2000.
38.
ZhouH, Randers-PehrsonG, GeardCR, BrennerDJ, HallEJ, HeiTK. Interaction between radiation-induced adaptive response and bystander mutagenesis in mammalian cells. Radiat Res160:512–516, 2003.
39.
DiPaoloJA, DonovanPJ, PopescuNC. Kinetics of Syrian hamster cells during x-irradiation enhancement of transformation in vitro by chemical carcinogen. Radiat Res66:310–325, 1976.
40.
DiPaoloJA, DonovanPJ. In vitro morphologic transformation of Syrian hamster cells by U.V.-irradiation is enhanced by X-irridation and unaffected by chemical carcinogens. Int J Radiat Biol Relat Stud Phys, Chem Med30:41–53, 1976.
41.
BorekC, ZaiderM, OngA, MasonH, WitzG.Ozone acts alone and synergistically with ionizing radiation to induce in vitro neoplastic transformation. Carcinogenesis7:1611–1613, 1986.
42.
PollockEJ, TodaroGJ. Radiation enhancement of SV40 transformation in 3T3 and human cells. Nature219:520–521, 1968.
43.
LittleJB. Influence of noncarcinogenic secondary factors on radiation carcinogenesis. Radiat Res87:240–250, 1981.
44.
PuckTT, MorseH, JohnsonR, WaldrenCA. Caffeine enhanced measurement of mutagenesis by low levels of gamma-irradiation in human lymphocytes. Somat Cell Mol Genet19:423–429, 1993.
45.
SuzukiK, KodamaS, WatanabeM.Extremely low-dose ionizing radiation causes activation of mitogen-activated protein kinase pathway and enhances proliferation of normal human diploid cells. Cancer Res61:5396–5401, 2001.
46.
RothkammK, LobrichM.From the cover: evidence for a lack of DNA double-strand break repair in human cells exposed to very low x-ray doses. Proc Natl Acad Sci U S A100:5057–5062, 2003.
47.
BrennerDJ, LittleJB, SachsRK. The bystander effect in radiation oncogenesis: II. A quantitative model. Radiat Res155:402–408, 2001.
48.
SchettinoG, FolkardM, PriseKM, VojnovicB, HeldKD, MichaelBD. Low-dose studies of bystander cell killing with targeted soft X rays. Radiat Res160:505–511, 2003.
49.
GrahamS, LevinML, LilienfeldAM, SchumanLM, GibsonR, DowdJE, HempelmannL.Preconception, intrauterine, and postnatal irradiation as related to leukemia. National Cancer Institute Monographs19:347–371, 1966.
50.
Ben-AmotzA, YatzivS, SelaM, GreenbergS, RachmilevichB, ShwarzmanM, WeshlerZ.Effect of natural beta-carotene supplementation in children exposed to radiation from the Chernobyl accident. Radiat Environ Biophys37:187–193, 1998.
51.
KorkinaLG, Afanas'efIB, DiplockAT. Antioxidant therapy in children affected by irradiation from the Chernobyl nuclear accident. Biochem Soc Trans21:314S, 1993.
