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An Introduction to Radioadaptive Response

S. M. Javad Mortazavi
Biology Division, Kyoto University of Education, Kyoto 612-8522, Japan


T he induction of the cytogenetic radioadaptive response in human lymphocytes by low doses of ionizing radiation was first reported by Olivieri et al. (1984). They reported that the frequency of chromatid aberrations were down to 50% less than they expected after exposure to 1.5 Gy of x-rays. Many articles have demonstrated radioadaptive response in plant cells (Cortes et al. 1990), insects (Fritz-Niggli and Schaeppi-Buechi 1991), Chinese hamster V79 cells (Ikushima 1987, 1989a, 1989b), cultured human lymphocytes (Wiencke et al. 1986, Shadley and Wolff 1987, Wolff et al. 1988, Shadley and Wiencke 1989, Sankaranaryanan 1989), embryonic and HeLa cells (Ishii and Watanabe 1996), occupationally exposed persons (Barquinero et al. 1995, Gourabi and Mozdarani 1998), cultured animal lymphocytes (Flores et al. 1996), and in vivo studies on laboratory animals (Wojcik and Tuschl 1990, Cai and Liu 1990, Farooqi and Kesavan 1993, Liu et al. 1992).
There are also reports indicating lack of radioadaptive response in cultured human lymphocytes (Bosi and Olivieri 1989, Olivieri and Bosi 1990, Hain et al. 1992). Furthermore, long-term follow up studies indicate that lack of radioadaptive response is not a temporary effect and in contrast with the early reports of Olivieri and Bosi (1990) does not depend on transient physiological factors (Mortazavi et al. 2000, Ikushima and Mortazavi 2000).

In Pharmacology:

when 2 drugs work together against one target; the produced effect may be:
1. less than the individual effects of the drug added together
2. equal to the individual effects of the drug added together
3. greater than the individual effects of the drug added together

2+2 => 3     Antagonism
2+2 => 4     Simple Additivity
2+2 => 5     Synergistic Effect

in other words:
Antagonism    The whole is smaller than the sum of its parts.
Additivity       The whole is equal to the sum of its parts.
Synergism      The whole is greater than the sum of its parts.

In Radiation Biology:
when cells are exposed to a high challenging dose (e.g. 1 Gy) after pretreatment with a low adapting or conditioning dose (e.g. 1 cGy); the produced effect may be:
1. less than the individual effects of the adapting and challenging doses (adaptive response).
2. equal to the individual effects of the adapting and challenging doses (additivity).
3. greater than the individual effects of the adapting and challenging doses (synergistic effect).

Preliminary results of the cytogenetical, immunological and hematological studies on the residents of high background radiation areas of Ramsar have been recently reported (Mortazavi et al. 2001, Ghiassi-Nejad et al. 2002 and Mortazavi et al. in press), suggesting that exposure to high levels of natural background radiation can induce radioadaptive response in human cells. Lymphocytes of Ramsar residents when subjected to 1.5 Gy of gamma rays showed fewer induced chromosome aberrations compared to residents in a nearby normal background control area whose lymphocytes were subjected to the same radiation dose.


Barquinero J.F., Barrios L., Caballin M.R., Miro R., Ribas M., Subias A. and Egozcue J. Occupational exposure to radiation induces an adaptive response in human lymphocytes, Int. J. Radiat. Biol., 67, 187-91, 1995.

Bosi A., and Olivieri G. Variability of the adaptive response to ionizing radiation in humans. Mutat. Res., 211, 13-17, 1989.

Cai L.and.Liu S.Z. Induction of cytogenetic adaptive response of somatic and germ cells in vivo and in vitro by low dose X-irradiation, Int. J. Radiat. Biol., 58, 187-194, 1990.

Cortes F, Dominguez I, Mateos S, Pinero J, Mateos JC. Evidence for an adaptive response to radiation damage in plant cells conditioned with X-rays or incorporated tritium. Int J Radiat Biol;57(3):537-41, 1990.

Farooqi, Z., Kesavan, , PC. Low-dose radiation-induced adaptive response in bone marrow cells of mice, Mutat. Res., 302, 83-9, 1993.

Flores M.J., Pinero J., Ortiz T., Pastor N., Mateos J.C. and Cortes F. Both bovine and rabbit lymphocytes conditioned with hydrogen peroxide show an adaptive response to radiation damage, Mutat. Res., 372, 9-15, 1996.

Gadhia P.K., Possible age-dependent adaptive response to a low dose of X-rays in human lymphocytes, Mutagenesis, 13, 151-152, 1998.

Gajendiran N, Tanaka K, Kumaravel TS, Kamada N. Neutron-induced adaptive response studied in go human lymphocytes using the comet assay. J Radiat Res (Tokyo), 42(1): 91-101, 2001.

Ghiassi-nejad, M; Mortazavi, SMJ; Cameron, JR; Niroomand-rad, A; Karam, PA; Very High Background Radiation Areas of Ramsar, Iran: Preliminary Biological Studies. Health Physics, 82(1): 87-93, 2002.

Gourabi H., and Mozdarani H. A cytokinesis-blocked micronucleus study of the radioadaptive response of lymphocytes of individuals occupationally exposed to chronic doses of radiation, Mutagenesis, 13, 475-80, 1998.

Hain J., Jaussi R., and Burkart W. Lack of adaptive response to low doses of ionizing radiation in human lymphocytes from five different donors. Mutat. Res., 283, 137-44, 1992.

Ikushima T. Chromosomal responses to ionizing radiation reminiscent of an adaptive response in cultured Chinese hamster cells, Mutation Research , Vol 180 , No 2 ,215-221 , 1987.

Ikushima T. Radioadaptive response: characterization of a cytogenetic repair induced by low-level ionizing radiation in cultured Chinese hamster cells, Mutation Research , Vol 227 , No 4 , 241-246 , 1989a.

Ikushima, T. Radioadaptive response: a novel chromosomal response in Chinese hamster cells in vitro, In: Chromosomal Aberrations, Basic and applied aspects, G. Obe and AT. Natarajan eds. Springer-Verlag, Berlin, pp. 151-161, 1989b.

Ikushima, T., and Mortazavi, S. M. J. Radioadaptive response: its variability in cultured human lymphocytes, In: Biological Effects of Low Dose Radiation. Yamada T, Mothersil C, Michael BD, and Potten CS, eds. Elsevier, Amsterdam, 1st edition, pp. 81-86, 2000.

Ishii K.and Watanabe M. Participation of gap-junctional cell communication on the adaptive response in human cells induced by low dose of X-rays, Int. J. Radiat. Biol. , 69: 291-9, 1996.

Liu S.Z., Cai L., Sun S.Q. Induction of a cytogenetic adaptive response by exposure of rabbits to very low dose-rate gamma-radiation, Int. J. Radiat. Biol., 62,187-90, 1992.

Mortazavi, S. M. J., Ikuhima T, Mozdarani H and Sharafi AA. Radiation Hormesis and Adaptive Responses Induced by Low Doses of Ionizing Radiation. Journal of Kerman University of Medical Sciences, Vol. 6, No. 1, 50-60, 1999.

Mortazavi, S. M. J., Ikuhima, T., Mozdarani, H., Sharafi, A. A. and Y. Ishi. Is low-level pre-irradiation of human lymphocytes an absolutely beneficial phenomenon. A report on the extra-ordinary synergism. Kowsar Medical Journal, Vol 5, No 4, 235-240, 2000.

Mortazavi S. M. J., Ghiassi Nejad M, and Beitollahi M.Very High Background Radiation Areas (VHBRAs) of Ramsar: Do We Need any Regulations to Protect the Inhabitants? Proceedings of the 34th midyear meeting, Radiation Safety and ALARA Considerations for the 21st Century, California, USA, 177-182, 2001.

Mortazavi S. M. Javad, Ghiassi-nejad M., Niroomand-rad Azam, Andrew Karam P., and Cameron John R. How should governments address high levels of natural radiation and radon? Lessons from the Chernobyl nuclear accident and Ramsar, Iran. Risk: Health, Safety and Environment, in press.

Olivieri G., Bodycote J. and Wolff S., Adaptive response of human lymphocytes to low concentrations of radioactive thymidine, Science, 223, 594-597, 1984.

Olivieri G., and Bosi A. Possible causes of variability of the adaptive response in human lymphocytes. In Chromosomal Aberrations Basic and Applied Aspects (G. Obe and E. D. induced DNA damage in adapted cells, Mutat. Res., 358,193-8, 1990.

Samson L.and Carins J., A new pathway for DNA repair in Escherichia coli, Nature, 267, 281-282, 1977. Samson L.and Schwartz J.L., Evidence for an adaptive DNA repair pathway in CHO and human skin fibroblast cell lines, Nature, 287, 861-863, 1980.

Sankaranarayanan K., Von Duyn A., Loos M., and Natarjan, A.T. Adaptive response of human lymphocytes to low level radiation from radioisotopes or X-rays. Mutat. Res., 211 , 7-12, 1989.

Shadley J.D.and Wiencke J.K. Induction of the adaptive response by X-rays is dependent on radiation intensity, Int. J. Radiat. Biol., 56, 107-118, 1989.

Shadley J.D., Wolff S. Very low doses of X-rays can cause human lymphocytes to become less susceptible to ionizing radiation, 2, 95-96, 1987.

Vijayalaxmi, Leal B.Z., Deahl T.S., Meltz M.L. Variability in adaptive response to low dose radiation in human blood lymphocytes: consistent results from chromosome aberrations and micronuclei. Mutat. Res., 348, 45-50, 1995.

Wiencke J.K., Afzal V., Olivieri G. and Wolff S. Evidence that the [3H] thymidine induced adaptive response of human lymphocytes to subsequent doses of X-rays involves the induction of chromosomal repair mechanism, Mutagenesis, 1, 375-380, 1986.

Wojcik A. and Tuschl H. Indications of an adaptive response in C57BL mice pre-exposed in vivo to low doses of ionizing radiation, Mutat. Res., 243, 67-73, 1990.

Wolff S., Afzal V., Wiencke J.K.and Olivieri G., Human lymphocytes exposed to low doses of ionizing radiation become refractory to high doses of radiation as well as to chemical mutagens that induce doublestrand breaks in DNA., Int. J. Radiat. Biol., 53 , 39-48, 1988.

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