Chromosomal Adaptive Response in Human Lymphocytes

Shadley, Jeff D.

doi:10.2307/3578750

Cited by 71 publications

(29 citation statements)

References 26 publications

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“…This adaptive response to IR, which occurs after exposures that are so low (0.005-0.01 Gy) that they do not induce discernible aberrations themselves, has been attributed to the induction of a repair mechanism that causes the restitution of X-rayinduced chromosome breaks (Wolff, 1998). Variations and the absence of adaptive responses have also been reported (Jacobson-Kram and Williams, 1988;Bauchinger et al, 1989;Bosi and Olivieri, 1989;Sankaranarayanan et al, 1989;Schmid et al, 1989;Hain et al, 1992;Müller et al, 1992;Wojcik et al, 1992Wojcik et al, , 1993Shadley, 1994;UNSCEAR, 1994;Vijayalaxmi et al, 1995;Boothman et al, 1996;Raaphorst and Boyden, 1999;Sorensen et al, 2002). Azzam et al (1996) exposed quiescent mouse fibroblasts (C3H 10T1/2) cells to doses of 1-100 mGy -rays and observed that the risk of neoplastic transformation was reduced from the spontaneous level to a rate three-to four-fold below that level.…”

Section: Studies Supporting or Refuting Toxicant-induced Adaptations mentioning

confidence: 94%

An Examination of Radiation Hormesis Mechanisms Using a Multistage Carcinogenesis Model

Schöllnberger

Stewart

Mitchel

et al. 2004

Nonlinearity in Biology, Toxicology, Medicine

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Section: Studies Supporting or Refuting Toxicant-induced Adaptations mentioning

confidence: 94%

An Examination of Radiation Hormesis Mechanisms Using a Multistage Carcinogenesis Model

Schöllnberger

Stewart

Mitchel

et al. 2004

Nonlinearity in Biology, Toxicology, Medicine

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“…Marcon et al (2003) showed that heavy smokers can repair DNA damage after the exposure to 2 Gy faster than non smokers or non-heavy smokers. Olivieri et al (1984) and Shadley (1994) suggested the existence of adaptive response that protects lymphocytes from oxidative damage. Smokers also showed lower levels of oxidised pyrimidinic bases in lymphocytes when compared to non-smokers (Berasati et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

The Influence of Individual Genome Sensitivity in DNA Damage Repair Assessment in Chronic Professional Exposure to Low Doses of Ionizing Radiation

Milić¹,

Rozgaj²,

Kašuba³

et al. 2011

Selected Topics in DNA Repair

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“…The delayed radioprotective effect can be considered a form of an adaptive response described originally as a phenomenon by which exposure of certain types of cells to a relatively low dose of radiation induces an enhanced resistance to the deleterious effects of a second but much larger dose of ionizing radiation (34,35). This phenomenon appears to require de novo protein synthesis since exposure of these cells to the protein synthesis inhibitor cyclohexamide after irradiation with the initial low radiation dose will inhibit the adaptive response to the second higher dose (36).…”

Section: Discussionmentioning

confidence: 99%

Maintenance of Manganese Superoxide Dismutase (SOD2)-Mediated Delayed Radioprotection Induced by Repeated Administration of the Free Thiol Form of Amifostine

Murley¹,

Nantajit

Baker³

et al. 2008

Radiation Research

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Thiol-containing drugs such as WR1065, the free thiol form of amifostine, have been shown to induce a delayed radioprotective effect in both malignant and non-malignant cells. In mammalian cells exposed to a dose as low as 40 μM WR1065, the redox-sensitive nuclear transcription factor κB (NFκB) is activated, leading to an elevation in the expression of the antioxidant gene manganese superoxide dismutase (SOD2) and a concomitant increase in active SOD2 enzyme levels that peaks 24 to 32 h later. Exposure of cells to ionizing radiation during the period of elevated SOD2 enzymatic activity results in an enhanced radiation resistance. This is seen as an increase in surviving fraction as determined by standard colony formation assays. To determine whether this delayed radioprotection can be maintained over a prolonged period in cells of either malignant or nonmalignant origin, both human microvascular endothelial cells (HMEC) and SA-NH mouse sarcoma cells were grown to confluence and exposed to 40 μM WR1065 using three administration protocols: (1) daily drug exposure for 10 days followed each day by irradiation with 2 Gy; (2) drug exposure once every 48 h followed by irradiation with 2 Gy 48 h later for 14 days; and (3) drug exposure every 72 h followed by irradiation with 2 Gy 72 h later for 12 days. As a function of each experimental condition, cell numbers and associated SOD2 enzymatic activities were measured at the time of each irradiation. None of the treatment conditions were toxic to either HMEC or SA-NH cells. SOD2 activity was elevated 5.3-and 1.8-fold over background on average for HMEC exposed to 40 μM WR1065 every 24 or 48 h, respectively. Likewise, SOD2 activity was elevated in SA-NH mouse sarcoma cells 7.8-and 4.9-fold after daily exposure to WR1065 or exposure to WR1065 once every 48 h, respectively. Both HMEC and SA-NH cells exhibited enhanced radiation resistance that correlated with the increase in SOD2 activity. The average respective increases in cell survival were 1.33 ± 0.01 (SEM), 1.23 ± 0.01 and 1.04 ± 0.01 for HMEC exposed to WR1065 every 24, 48 and 72 h, respectively, and 1.27 ± 0.01, 1.18 ± 0.02 and 1.02 ± 0.02 for SA-NH cells exposed to WR1065 every 24, 48 and 72 h, respectively. Both the elevation in WR1065-induced SOD2 enzymatic activity and the corresponding increase in radiation resistance were completely inhibited in HMEC and SA-NH cells transfected with human or mouse SOD2 siRNA oligomers and irradiated 24 h later. These data demonstrate that a delayed radioprotective effect can be induced and maintained over a prolonged period in both non-malignant and malignant cells exposed to thiol-containing drugs such as WR1065. For non-malignant cells this represents a novel paradigm for radiation protection. The ability of WR1065 to induce a persistent elevated radiation resistance in malignant cells, however,

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Chromosomal Adaptive Response in Human Lymphocytes

Cited by 71 publications

References 26 publications

An Examination of Radiation Hormesis Mechanisms Using a Multistage Carcinogenesis Model

An Examination of Radiation Hormesis Mechanisms Using a Multistage Carcinogenesis Model

The Influence of Individual Genome Sensitivity in DNA Damage Repair Assessment in Chronic Professional Exposure to Low Doses of Ionizing Radiation

Maintenance of Manganese Superoxide Dismutase (SOD2)-Mediated Delayed Radioprotection Induced by Repeated Administration of the Free Thiol Form of Amifostine

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