Adaptive response to DNA and chromosomal damage induced by X-rays in human blood lymphocytes

Abstract

Nucleoid sedimentation, single-cell gel electrophoresis (comet assay) and premature chromosome condensation (PCC) technique were utilized to estimate the involvement of DNA strand breaks and chromosomal damage in radio-adaptive response of stimulated human lymphocytes. Conditioning of cells with 0.02 Gy X-rays rendered them more resistant to single- and double-strand DNA breaks produced by 1 Gy challenging treatment as revealed by the sedimentation behaviour of the nucleoids and the comet assay. Nucleoid sedimentation also demonstrated that adaptive reaction towards X-ray-induced DNA damage is favoured in the presence of oxygen. A concomitant decrease in the amount of interphase chromosomal breaks visualized by PCC under the same experimental conditions was observed. Data indicate that adaptation of human lymphocytes to X-rays is tightly linked to the reduced susceptibility towards generation of DNA and chromosomal breaks. It is proposed that the very persistence of DNA strand discontinuities might serve as a triggering signal for the adaptation of human lymphocytes against ionizing radiation exposure.

A brief review of radiation hormesis

“…For both doses there was a statistically higher frequency of repair for the primed cells when compared with the control, indicating a positive stimulation from the initial priming dose 22 . A similar response has been observed in human lymphocytes 23 . After a prime dose of 20 mGy, the lymphocytes showed a resistance to both double and single strand breaks induced by a 1 Gy challenge dose at times of 9 and 30 hours after initial irradiation.…”

“…Many studies show adaptive responses on a molecular, cellular, organ and organism level following an initial primed dose and consequently higher resistance to mid-lethal challenge doses and also to non-radiogenic toxins [21][22][23]34,35,47,64 . Resistance has also been seen at specific times post initial irradiation during which the induced resistance also may operate against nonradiogenic, i.e., spontaneous cancer.…”

“…After a prime dose of 20 mGy, the lymphocytes showed a resistance to both double and single strand breaks induced by a 1 Gy challenge dose at times of 9 and 30 hours after initial irradiation. It has been suggested that the physical reason for this type of response comes from the induced production of specific proteins that aid in DNA repair, following the initial low dose primer 23 .…”

Adaptive response: some underlying mechanisms and open questions

“…An adaptive response to radiation also occurs in human lymphocytes (Shadley and Wolff, 1987;Wojewózka et al, 1996;Stoilov et al, 2007). This was first demonstrated by Olivieri et al (1984) when peripheral blood lymphocytes were irradiated with low doses of X-rays or exposed to tritium labeled thymidine and a lower than expected frequency of chromosomal aberrations was found after a subsequent higher test (or challenge) dose.…”

“…Low levels of damage could be triggering events that signal the activation of DNA repair systems (Boreham and Mitchel, 1991;Wolff, 1998;Matsumoto et al, 2004). For example, the persistence of DNA strand discontinuities could serve as a triggering signal for the adaptation of human lymphocytes against ionizing radiation exposure (Stoilov et al, 2007). The magnitude of the AR has been shown to increase with the dose of radiation up to a certain threshold (Bryant, 1976).…”