High expression of the circadian gene mPer2 diminishes the radiosensitivity of NIH 3T3 cells

Chang, Le; Liu, Y.Y.; Zhu, Bin; Li, Y.; Hua, Hui; Wang, Y.H.; Zhang, J.; Jiang, Zhou; Wang, Z.R.

doi:10.1590/s0100-879x2009005000022

Cited by 5 publications

(4 citation statements)

References 39 publications

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“…At the time of exposure to DNA damage, the CCD-34Lu cells were non-proliferating and stimulated after IR to enter the cell cycle to originate colonies. Study results demonstrating that cells irradiated at the trough and not at the peak of PER2 were affected with regard to their clonogenic capacity concord with reports showing increased sensitivity to γ radiation in Per2 mutant mice (Fu et al 2002) and decreased radio sensitivity in proliferating NIH 3T3 fibroblasts overexpressing mPer2 (Chang et al 2009). But data regarding clonogenic survival in clock-altered cells exposed to genotoxic stress showed quite a different picture.…”

Section: Discussionsupporting

confidence: 80%

Analysis of DNA-damage response to ionizing radiation in serum-shock synchronized human fibroblasts

Corrà

Bee

et al. 2017

Cell Biol Toxicol

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Many aspects of cellular physiology, including cellular response to genotoxic stress, are related to the circadian rhythmicity induced by the molecular clock. The current study investigated if the cellular response to DNA damage is in relation to endogenous expression levels of the PER2 protein, a key component of the molecular regulatory system that confers rhythmicity in mammalian cells. Human normal fibroblasts (CCD-34Lu) were subjected to serum shock to induce circadian oscillations of the PER2 protein and then irradiated with γ- rays at times corresponding to the trough and peak expression of the PER2 protein. To better examine cellular response to DNA damage, the experiments performed in this study were carried out in non-proliferating CCD-34Lu fibroblasts in order to maintain the cell and circadian cycles separated while they were being exposed to genotoxic stress. Study results demonstrated that clonogenic cell survival, double-strand break repair kinetics, and TP53 protein levels were affected in the cells irradiated at the trough than in those irradiated at peak expression of the PER2 protein.Electronic supplementary materialThe online version of this article (doi:10.1007/s10565-017-9394-9) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 80%

Analysis of DNA-damage response to ionizing radiation in serum-shock synchronized human fibroblasts

Corrà

Bee

et al. 2017

Cell Biol Toxicol

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“…This was taken as a hint for a contribution of the cellular oscillator to radioprotection. In fact, overexpression of Per2 was shown to diminish radiosensitivity in 3T3 cells [123]. The same was also observed in tumor cells [124].…”

Section: Oscillator Proteins and Health: Polymorphisms Gene Silencinmentioning

confidence: 85%

Melatonin, the circadian multioscillator system and health: the need for detailed analyses of peripheral melatonin signaling

Hardeland

Madrid

Tan

et al. 2011

Journal of Pineal Research

388

339

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: Evidence is accumulating regarding the importance of circadian core oscillators, several associated factors, and melatonin signaling in the maintenance of health. Dysfunction of endogenous clocks, melatonin receptor polymorphisms, age‐ and disease‐associated declines of melatonin likely contribute to numerous diseases including cancer, metabolic syndrome, diabetes type 2, hypertension, and several mood and cognitive disorders. Consequences of gene silencing, overexpression, gene polymorphisms, and deviant expression levels in diseases are summarized. The circadian system is a complex network of central and peripheral oscillators, some of them being relatively independent of the pacemaker, the suprachiasmatic nucleus. Actions of melatonin on peripheral oscillators are poorly understood. Various lines of evidence indicate that these clocks are also influenced or phase‐reset by melatonin. This includes phase differences of core oscillator gene expression under impaired melatonin signaling, effects of melatonin and melatonin receptor knockouts on oscillator mRNAs or proteins. Cross‐connections between melatonin signaling pathways and oscillator proteins, including associated factors, are discussed in this review. The high complexity of the multioscillator system comprises alternate or parallel oscillators based on orthologs and paralogs of the core components and a high number of associated factors with varying tissue‐specific importance, which offers numerous possibilities for interactions with melatonin. It is an aim of this review to stimulate research on melatonin signaling in peripheral tissues. This should not be restricted to primary signal molecules but rather include various secondarily connected pathways and discriminate between direct effects of the pineal indoleamine at the target organ and others mediated by modulation of oscillators.

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“…Overexpression of PER2 in human pancreatic cells not only inhibited cell growth, but also sensitized them to cisplatin 17 . At the same time, some contradictory reports have demonstrated that LLC and EMT6 18 and NIH-3T3 19 cells with high levels of PER2 expression show increased resistance to ionizing radiation. Based on these data, it was suggested that PER2 acts as an inhibitor in tumor radiotherapy.…”

Section: Discussionmentioning

confidence: 99%

Deficiency in PER proteins has no effect on the rate of spontaneous and radiation-induced carcinogenesis

et al. 2013

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There is a growing body of evidence that components of the circadian clock are involved in modulation of numerous signaling pathways, and that clock deregulation due to environmental or genetic factors contributes to the development of various pathologies, including cancer. Previous work performed in tissue culture and in in vivo mouse models defined mammalian PERIOD proteins as tumor suppressors, although some experimental inconsistencies (the use of mice on mixed genetic background, lack of sexual discrimination) did not allow a definitive conclusion. To address this issue in a systematic way, we performed a detailed analysis comparing the incidence of tumor development after low-dose ionizing radiation in male and female wild-type, Per1−/−, and Per2−/− mice. We showed that in contrast to previous reports deficiency in either Per1 or Per2 genes by itself does not make mice more tumor-prone; moreover, some of the long-term effects of ionizing radiation in Per2-deficient mice are reminiscent more of accelerated aging rather than tumor-prone phenotype. Our histopathological analysis also revealed significant sexual dimorphism both in the rate of radiation-induced tumorigenesis and in the spectrum of tumors developed, which underscores the importance of using sex-matched experimental groups for in vivo studies. Based on our results, we suggest that the role of PER proteins as bona fide tumor suppressors needs to be reevaluated.

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High expression of the circadian gene mPer2 diminishes the radiosensitivity of NIH 3T3 cells

Cited by 5 publications

References 39 publications

Analysis of DNA-damage response to ionizing radiation in serum-shock synchronized human fibroblasts

Analysis of DNA-damage response to ionizing radiation in serum-shock synchronized human fibroblasts

Melatonin, the circadian multioscillator system and health: the need for detailed analyses of peripheral melatonin signaling

Deficiency in PER proteins has no effect on the rate of spontaneous and radiation-induced carcinogenesis

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