Abstract
Chromosome damage and the spectrum of aberrations induced by low doses of γ-irradiation, X-rays and accelerated carbon ions (195 MeV/u, LET 16.6 keV/μm) in peripheral blood lymphocytes of four donors were studied. G0-lymphocytes were exposed to 1–100 cGy, stimulated by PHA, and analyzed for chromosome aberrations at 48 h post-irradiation by the metaphase method. A complex nonlinear dose–effect dependence was observed over the range of 1 to 50 cGy. At 1–7 cGy, the cells showed the highest radiosensitivity per unit dose (hypersensitivity, HRS), which was mainly due to chromatid-type aberration. According to the classical theory of aberration formation, chromatid-type aberrations should not be induced by irradiation of unstimulated lymphocytes. With increasing dose, the frequency of aberrations decreased significantly, and in some cases it even reached the control level. At above 50 cGy the dose–effect curves became linear. In this dose range, the frequency of chromatid aberrations remained at a low constant level, while the chromosome-type aberrations increased linearly with dose. The high yield of chromatid-type aberrations observed in our experiments at low doses confirms the idea that the molecular mechanisms which underlie the HRS phenotype may differ from the classical mechanisms of radiation-induced aberration formation. The data presented, as well as recent literature data on bystander effects and genetic instability expressed as chromatid-type aberrations on a chromosomal level, are discussed with respect to possible common mechanisms underlying all low-dose phenomena.
References
Kahdim MA, Moore SR, Goodwin EH (2004) Interrelationships amongst radiation-induced genomic instability, bystander effects, and the adaptive response. Mutat Res 568:21–32
Mothersill C, Seymour CB, Joiner MC (2002) Relationship between radiation-induced low-dose hypersensitivity and the bystander effect. Radiat Res 157:526–532
Joiner MC, Marples B, Lambin P, Short SC, Turesson I (2001) Low-dose hypersensitivity: current status and possible mechanisms. Int J Radiat Oncol Biol Phys 49:379–389
Marples B, Wouters BG, Collis SJ, Chalmers AJ, Joiner MC (2004) Low-dose hyper-radiosensitivity: a consequence of ineffective cell cycle arrest of radiation-damaged G2-phase cells. Radiat Res 161:247–255
Shmakova NL, Fadeeva TA, Krasavin EA, Komochkov MM, Abouzeid OA (1999) Cytogenetic effects of low dose radiation in Chinese hamster cells. Nucleonica 44:529–548
Shmakova NL, Fadeeva TA, Nasonova EA, Krasavin EA, Rzyanina AV (2002) Cytogenetic effects of low dose radiation in mammalian cells: the analysis of the phenomenon of hypersensitivity and induced radioresistance (Russian). Radiat Biol Radioecol 42:245–250
Krasavin EA, Govorun RD, Shmakova NL, Koshlan’ IV, Nasonova EA, Repin MV (2004) Genetic action of radiation with different physical characteristics on mammalian cells. In: Kadyshevsky VG (eds) Physics of particles and nuclei, vol 35. Pleiades Publishing, Inc., pp 797–813
Nasonova EA, Füssel K, Berger S, Gudowska-Nowak E, Ritter S (2004) Cell cycle arrest and aberration yield in normal human fibroblasts. I. Effects of X-rays and 195 MeV u−1 C ions. Int J Radiat Biol 80:621–634
Savage JRK (1975) Classification and relationships of induced chromosomal structural changes. J Med Genet 12:103–122
Lloyd DC, Edwards AA, Leonard A, Deknudt GL, Verschaeve L, Natarajan AT, Darroudi F, Obe G, Palitti F, Tanzarella C, Tawn EJ (1992) Chromosomal aberrations in human lymphocytes induced in vitro by very low doses of X-rays. Int J Radiat Biol 61:335–343
Mothersill C, Seymour CB (2006) Radiation-induced bystander effects and the DNA paradigm: an “out of the field” perspective. Mutat Res 597:5–10
Böhrnsen G, Weber KJ, Scholz M (2002) Measurement of biological effects of high-energy carbon ions at low doses using semi-automated cell detection system. Int J Radiat Biol 78:259–266
Duell Th, Lengfelder E, Fink R, Giesen R, Bauchinger M (1995) Effect of activated oxygen species in human lymphocytes. Mutat Res 336:29–38
Pollycove M, Feinendegen LE (2003) Radiation-induced versus endogenous DNA damage: possible effect of inducible protective responses in mitigating endogenous damage. Hum Exp Toxicol 22:290–306
Kadhim MA, Marsden SJ, Malcolmson AM, Folkard M, Goodhead DT, Prise KM, Michael BD (2001) Long-term genomic instability in human lymphocytes induced by single-particle irradiation. Radiat Res 155:122–126
Ponnaiya B, Jenkins-Baker G, Bigelow A, Marino S, Geard CR (2004) Detection of chromosomal instability in α-irradiated and bystander human fibroblasts. Mutat Res 568:41–48
Turker MS, Schwartz JL, Jordan R, Ponomareva ON, Connolly L, Kasameyer E, Lasarev M, Clepper L (2004) Persistence of chromatid aberrations in the cells of solid mouse tissues exposed to 137Cs gamma radiation. Radiat Res 162:357–364
Rugo RE, Schiestl RH (2004) Increase in oxydative stress in the progeny of X-irradiated cells. Radiat Res 162:416–425
Limoli CL, Giedzinski E, Morgan WF, Swarts SG, Jones GDD, Hyun W (2003) Persistent oxidative stress in chromosomally unstable cells. Cancer Res 63:3107–3111
Tominaga H, Kodama S, Matsuda N, Suzuki K, Watanabe M (2004) Involvement of reactive oxygen species (ROS) in the induction of genetic instability by radiation. J Radiat Res 45:181–188
Clutton SM, Townsend KMS, Walker C, Ansell JD, Wright EG (1996) Radiation-induced genetic instability and persisting oxidative stress in primary bone marrow cultures. Carcinogenesis 17:1633–1639
Samper E, Nicholls DG, Melov S (2003) Mitochondrial oxidative stress causes chromosomal instability of mouse embryonic fibroblasts. Aging Cell 2:277–285
Leach JK, Tuyle GV, Lin P-S, Schmidt-Ulrich P, Mikkelsen RB (2001) Ionizing radiation-induced, mitochondria-dependent generation of reactive oxygen/nitrogen. Cancer Res 61:3894–3901
Ogawa Y, Takahashi T, Kobayashi T, Toda M, Nishioka A, Kariya S, Segushi H, Yamamoto H, Yoshida S (2003) Comparison of radiation-induced reactive oxygen species formation in adult articul chondrocytes and that in human peripheral T cells: possible implication in radiosensitivity. Int J Mol Med 11:455–459
Kawamura S, Takai D, Watanabe K, Hayashi J, Hayakawa K, Akashi M (2005) Role of mitochondrial DNA in cells exposed to irradiation: generation of reactive oxygen species (ROS) is required for G2 checkpoint upon radiation. J Health Sci 51:385–393
Suzuki K, Kodama S, Watanabe M (2001) Extremely low-dose ionizing radiation causes activation of mitogen-activated protein kinase pathway and enhances proliferation of normal human diploid cells. Cancer Res 61:5396–5401
Shonai T, Adachi M, Sakata K, Takewaka M, Endo T, Imai K, Hareyama M (2002) MEK/ERK pathway protect c ionizing radiation-induced loss of mitochondrial mambrane potential and cell death in lymphocytic leukemia cells. Cell Death Differ 9:963–971
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Nasonova, E.A., Shmakova, N.L., Komova, O.V. et al. Cytogenetic effects of low-dose radiation with different LET in human peripheral blood lymphocytes. Radiat Environ Biophys 45, 307–312 (2006). https://doi.org/10.1007/s00411-006-0073-0
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DOI: https://doi.org/10.1007/s00411-006-0073-0