Low-dose carbon ion irradiation effects on DNA damage and oxidative stress in the mouse testis
TL;DR: In this paper, the effects of low-dose carbon ion irradiation on reproductive system of mice were investigated by measuring DNA double-strand breaks (DNA DSBs) and oxidative stress parameters including malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, and testis weight and sperm count at 12h, 21d and 35d after irradiation in mouse testis.
About: This article is published in Advances in Space Research.The article was published on 2011-01-04. It has received 9 citations till now. The article focuses on the topics: DNA damage & Oxidative stress.
Citations
More filters
TL;DR: TiO2 NP exposure resulted in lesions of testis and epididymis, deductions in sperm concentration and sperm motility, and an increase of the number of abnormal sperm in mice, implying that spermatogenesis suppression caused by TiO2NP exposure may be associated with alterations of testicular marked enzymes and oxidative stress in the testes.
Abstract: TiO2 nanoparticles (NPs) have been demonstrated to suppress spermatogenesis in animals, while there is little data related to the biochemical dysfunctions during spermatogenesis due to exposure to TiO2 NPs. In this study, male mice have been exposed to TiO2 NPs via intragastric administration for 60 consecutive days. The findings showed that TiO2 NP exposure resulted in lesions of testis and epididymis, deductions in sperm concentration and sperm motility, and an increase of the number of abnormal sperm in mice. Furthermore, TiO2 NP exposure with 2.5, 5, or 10 mg/kgbw decreased activities of lactate dehydrogenase (-11.59% to -39.84%), sorbitol dehydrogenase (-23.56% to -57.33%), succinate dehydrogenase (-27.04% to -57.85%), glucose-6-phosphate dehydrogenase (-28.3% to -56.42%), Na(+)/K(+)-ATPase (-15.59% to -53.11%), Ca(2+)-ATPase (-12.44% to -55.41%), and Ca(2+)/Mg(2+)-ATPase (-28.25% to -65.72%), and elevated activities of acid phosphatase (+10.48% to +40.0%), alkaline phosphatase (+20.65% to +64.07%), and total nitric oxide synthase (+0.68- to +2.3-fold) in the testes of mice, respectively. In addition, TiO2 NP exposure caused excessive production of reactive oxygen species (+16.15% to +110.62%), and increased malondialdehyde of lipid peroxidation product (+38.96% to +118.07%), carbonyl of protein oxidative product (+20.98% to +108.1%), and 8-hydroxydeoxyguanosine of DNA oxidative product (+0.9- to +1.83-fold) in the testes, respectively. It implied that spermatogenesis suppression caused by TiO2 NP exposure may be associated with alterations of testicular marked enzymes and oxidative stress in the testes.
59 citations
TL;DR: Departure of DNA‐PKcs in glioblastoma cells at least partly suppressed IR‐inflicted migration, invasion, and tube formation of HMEC‐1 cells, which may be associated with the reduced HIF‐1α level and VEGF secretion.
Abstract: DNA-dependent protein kinase catalytic subunit (DNA-PKcs) plays a critical role in non-homologous end-joining repair of DNA double-strand breaks (DSB) induced by ionizing radiation (IR). Little is known, however, regarding the relationship between DNA-PKcs and IR-induced angiogenesis; thus, in this study we aimed to further elucidate this relationship. Our findings revealed that lack of DNA-PKcs expression or activity sensitized glioma cells to radiation due to the defective DNA DSB repairs and inhibition of phosphorylated Akt(Ser473) . Moreover, DNA-PKcs deficiency apparently mitigated IR-induced migration, invasion and tube formation of human microvascular endothelial cell (HMEC-1) in conditioned media derived from irradiated DNA-PKcs mutant M059J glioma cells or M059K glioma cells that have inhibited DNA-PKcs kinase activity due to the specific inhibitor NU7026 or siRNA knockdown. Moreover, IR-elevated vascular endothelial growth factor (VEGF) secretion was abrogated by DNA-PKcs suppression. Supplemental VEGF antibody to irradiated-conditioned media was negated enhanced cell motility with a concomitant decrease in phosphorylation of the FAK(Try925) and Src(Try416) . Furthermore, DNA-PKcs suppression was markedly abrogated in IR-induced transcription factor hypoxia inducible factor-1α (HIF-1α) accumulation, which is related to activation of VEGF transcription. These findings, taken together, demonstrate that depletion of DNA-PKcs in glioblastoma cells at least partly suppressed IR-inflicted migration, invasion, and tube formation of HMEC-1 cells, which may be associated with the reduced HIF-1α level and VEGF secretion. Inhibition of DNA-PKcs may be a promising therapeutic approach to enhance radio-therapeutic efficacy for glioblastoma by hindering its angiogenesis.
34 citations
Cites methods from "Low-dose carbon ion irradiation eff..."
...Neutral comet assays Comet assay were performed as previously described (Liu et al., 2011)....
[...]
TL;DR: It is demonstrated that simulated microgravity and CIR can induce spermatogenic cell apoptosis and sperm DNA damage, which may be one of the underlying mechanisms behind male fertility decline under space environment.
29 citations
TL;DR: Results suggested that carbon-ion irradiation induced apoptosis through the p53 pathway in zebrafish eyes independent of ROS generation, suggesting that Irradiation at high doses may disrupt eye development of zebra fish embryos.
14 citations
TL;DR: A vulval tissue model of Caenorhabditis elegans was for the first time used to assess RCD in vivo induced by carbon-ion irradiation, and an increased induction of RCD was observed in the worms impaired in homologous recombination (HR), but not in non-homologous end jointing pathway, suggesting a crucial role of HR repair in vulval cells of C. elegans in dealing with the carbon-ions-induced DNA damage.
7 citations
References
More filters
TL;DR: A public domain program under the GNU license for PC computers is developed that can be run on a variety of hardware and software platforms and was tested on human lymphocytes exposed to gamma-rays and found to yield reproducible results.
Abstract: The single-cell gel electrophoresis, also known as the comet assay, has gained wide-spread popularity as a simple and reliable method to measure genotoxic and cytotoxic effects of physical and chemical agents as well as kinetics of DNA repair. Cells are generally stained with fluorescent dyes. The analysis of comets--damaged cells which form a typical comet-shaped pattern--is greatly facilitated by the use of a computer image-analysis program. Although several image-analysis programs are available commercially, they are expensive and their source codes are not provided. For Macintosh computers a cost-free public domain macro is available on the Internet. No ready for use, cost-free program exists for the PC platform. We have, therefore, developed such a public domain program under the GNU license for PC computers. The program is called CASP and can be run on a variety of hardware and software platforms. Its practical merit was tested on human lymphocytes exposed to gamma-rays and found to yield reproducible results. The binaries for Windows 95 and Linux, together with the source code can be obtained from: http://www.casp.of.pl.
680 citations
TL;DR: While the induction of oxidative stress in spermatozoa is causally involved in the aetiology of male infertility, the prospects of using such a strategy for male contraception is fraught with potential problems, should the suppression of fertility be incomplete and DNA-damaged spermatozosa gain access to the oocyte.
458 citations
Book•
01 Jan 1977
TL;DR: This book consists of 39 chapters and some of the titles are: Bacillus subtilis repair test, Induced reversion using human adenovirus, The fluctuation test in bacteria, Chemical mutagenesis with diploid human fibroblasts, The specific locus test in the mouse, The bone marrow micronucleus test, and Sperm morphology in testing in mice.
Abstract: This book consists of 39 chapters. Some of the titles are: Bacillus subtilis repair test, Induced reversion using human adenovirus, The fluctuation test in bacteria, Chemical mutagenesis with diploid human fibroblasts, The specific locus test in the mouse, The bone marrow micronucleus test, and Sperm morphology in testing in mice.
442 citations
TL;DR: There is an excellent correlation between the efficiency of exponential (single-hit) cell killing and the induction of non-rejoining DNA strand breaks, as measured on alkaline sucrose gradients, which implies that non- rejoined breaks are a cause of cell death.
Abstract: THE mechanisms by which mammalian cells are killed by ionising radiation have not been explained at the molecular level and radiations with a high linear energy transfer (LET) can provide an important tool for investing these mechanisms. High-LET radiations, such as neutrons, π-mesons and low-energy heavy ions are known to kill bacteria1,2, yeast3,4, and mammalian cells in vitro5–9 more efficiently per unit dose than radiations with diffuse patterns of ionization, or low-LETs, such as γ or X rays. Other radiobiological phenomena associated with high-LET radiations are a reduced effect of chemical modifiers, for example, oxygen10, on cellular radiation sensitivity and reduction or loss of cellular ability to recover from radiation damage between split radiation doses5,8. Because of these and other attributes, including the favourable depth–dose distribution of heavy ions and π-mesons, high-LET radiations are being actively considered for use in cancer radiation therapy11,12, and a thorough understanding of their biological effects is necessary for them to be used to advantage clinically. We report here that, over an LET range of 1–1953 KeV µm−1, there is an excellent correlation between the efficiency of exponential (single-hit) cell killing and the induction of non-rejoining DNA strand breaks, as measured on alkaline sucrose gradients. This correlation implies that non-rejoined breaks are a cause of cell death.
361 citations
"Low-dose carbon ion irradiation eff..." refers background in this paper
...For example, heavy ions produce more irreparable DNA breaks (Ritter et al., 1997), chromosomal breakage and rearrangements and a greater degree of abnormal differentiation (Sekine et al....
[...]
TL;DR: A brief review of selected examples of results of toxic exposures in genetically deficient animal models are discussed to highlight the roles of p53 and the Fas system as modulators of proapoptotic activity in the testis.
Abstract: Azoospermia and long-lasting testicular atrophy are common adverse consequences of cancer treatment. Chemotherapeutic agents may disrupt spermatogenesis by targeting various testicular cell types (Leydig cells, Sertoli cells, and germ cells) and by activating numerous molecular pathways involved in germ cell life-and-death decision making. Genetically modified animal models with deficiencies in specific proapoptotic and prosurvival pathways have become powerful tools in understanding the molecular regulation of spermatogenesis and the response of the seminiferous epithelium to toxic injury. In this brief review, selected examples of results of toxic exposures in genetically deficient animal models are discussed to highlight the roles of p53 and the Fas system as modulators of proapoptotic activity in the testis. A final section focuses on cisplatin, a cancer chemotherapeutic agent that produces male reproductive toxicity by targeting multiple cell types in the testis.
178 citations