DNA damage and its repair in lymphocytes and thyroid nodule cells during radioiodine therapy in patients with hyperthyroidism

Grzesiuk, Wiesław; Nieminuszczy, Jadwiga; Kruszewski, Marcin; Iwanienko, Teresa; Płazińska, Maria Teresa; Bogdańska, Magdalena; Bar-Andziak, Ewa; Królicki, Leszek; Grzesiuk, Elżbieta

doi:10.1677/jme.1.02174

Cited by 5 publications

(3 citation statements)

References 17 publications

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“…Although comet assay is very well suited to the in vivo DNA damage investigation (Burlinson et al, 2007), a considerable differences were observed between different donor animals in course of this study (Table 2). Similar high diversity in DNA damage has been reported previously between human blood donors (Grzesiuk et al, 2006) and can be explained by differences in everyday individual behaviour of blood donors (for review, see Møller, 2000). The diet with transgenic triticale did not affect in this experiment the postnatal growth and development of mice and polymerase chain reaction used to analyses several tissues did not show the presence of transgenic DNA (PCR product of 637 bp) in any of the examined tissues: blood, kidney, liver, spleen and thigh muscle (Baranowski et al, 2006).…”

Section: Resultssupporting

confidence: 77%

Micronucleus test and comet assay on mice fed over five generations a diet containing genetically modified triticale

et al. 2008

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One of the concerns regarding the common use of genetically modifi ed (GM) feed in animal nutrition is that transgenic sequences may have a negative effect on the organism or (and) its cells. The present report assesses the genotoxic potential effect of a diet containing GM triticale on mice by using micronuclei test and comet assay. One group of mice (C57 Bl/6J strain) were fed continuously over fi ve generations a pelleted diet containing 20% of GM triticale (tolerant to phosphinothricine) grain, while the control group was fed pellets with 20% conventional triticale grain. Ten 91-days-old mice (fi ve females and fi ve males) were randomly selected from each group and each generation for micronuclei test in bone marrow and peripheral blood erythrocytes and the some number of mice was used for comet assay. The results obtained did not reveal any statistically signifi cant differences in the micronuclei frequency nor any other DNA damage between the control and experimental groups of mice in all fi ve generations. Thus, it seems evident that the diet containing GM triticale (with bar transgene) does not induce chromosome damage, nor has it any effect on the formation of DNA breaks or base lesions.

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Section: Resultssupporting

confidence: 77%

Micronucleus test and comet assay on mice fed over five generations a diet containing genetically modified triticale

et al. 2008

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“…Beside the genotoxic effects of toxic elements (especially metals), DNA damaging effects of radionuclides (although their concentrations in the transport water were extremely low) should not be neglected. The ability of radionuclides to induce primary DNA damage in terms of single and double strand breaks is well documented in earlier in vitro and in vivo studies (Pedraza Lopez et al, 2000;Calini et al, 2002;Kopjar and Garaj-Vrhovac, 2005;Grzesiuk et al, 2006;Morita et al, 1992). Therefore, when discussing the overall levels of damage as recorded by the alkaline comet assay, possible synergistic effects of heavy metals and radionuclides should also be anticipated.…”

Section: Discussionmentioning

confidence: 92%

The assessment of genotoxic effects of wastewater from a fertilizer factory

Durgo

Oreščanin²,

Lulić

et al. 2008

J of Applied Toxicology

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In this study we investigated cytotoxic, mutagenic and genotoxic effects of different concentrations of wastewater from the phosphoric gypsum depot near the factory for fertilizing agents 'INA Petrokemija' (Kutina, Croatia). The Ames test was performed on Salmonella typhimurium TA98 and TA100 strains, in the presence of S9 mix, glutathione and buffer, respectively. Cytotoxicity was studied on human laryngeal carcinoma cells (HEp2) and human cervical cells (HeLa). The level of lipid peroxidation in these two cell lines was evaluated in parallel. To establish the levels of primary DNA damage, the alkaline comet assay was performed on treated human peripheral blood leukocytes. No mutagenic effects of phosphoric gypsum on Salmonella typhimurium strains in the presence of S9 mix, GSH or PBS were observed. However, strong cytotoxic effect was observed on both human cell lines when they were treated with different concentrations of wastewater. Lipid peroxidation was induced and increased by prolonged time of incubation, highlighting that the damage was not repaired, but increased with the time of incubation. The results of the alkaline comet assay indicate significant DNA damaging potential of wastewater for human leukocytes. Since phosphoric gypsum transport water in its present composition and acidity is highly toxic and acts as prooxidant, causing free radicals formation and DNA damage, urgent neutralization/purification of the wastewater to a level acceptable for disposal into the environment is mandatory.

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“…In thyroid cells, I-131 induces DSBs detectable as γH2AX or 53BP1 foci (Hershman et al . 2011), as well as clustered DNA damage detected by Comet assay (Grzesiuk et al . 2006).…”

Section: Discussionmentioning

confidence: 99%

Formation of carcinogenic chromosomal rearrangements in human thyroid cells after induction of double-strand DNA breaks by restriction endonucleases

Evdokimova¹,

Gandhi²,

Rayapureddi³

et al. 2012

Endocrine-Related Cancer

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Ionizing radiation (IR) exposure increases the risk of thyroid cancer and other cancer types. Chromosomal rearrangements, such as RET/PTC, are characteristic features of radiation-associated thyroid cancer and can be induced by radiation in vitro. IR causes double-strand breaks (DSBs), suggesting that such damage leads to RET/PTC, but the rearrangement mechanism has not been established. To study the mechanism, we explored the possibility of inducing RET/PTC by electroporation of restriction endonucleases (REs) into HTori-3 human thyroid cells. We used five REs, which induced DSB in a dose-dependent manner similar to that seen with IR. Although all but one RE caused DSB in one or more of the three genes involved in RET/PTC, rearrangement was detected only in cells electroporated with either PvuII (25 and 100 U) or StuI (100 and 250 U). The predominant rearrangement type was RET/PTC3, which is characteristic of human thyroid cancer arising early after Chernobyl-related radioactive iodine exposure. Both enzymes that produced RET/PTC had restriction sites only in one of the two fusion partner genes. Moreover, the two enzymes that produced RET/PTC had restriction sites present in clusters, which was not the case for RE that failed to induce RET/PTC. In summary, we establish a model of DSB induction by RE and report for the first time the formation of carcinogenic chromosomal rearrangements, predominantly RET/PTC3, as a result of DSB produced by RE. Our data also raise a possibility that RET/PTC rearrangement can be initiated by a complex DSB that is induced in one of the fusion partner genes.

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DNA damage and its repair in lymphocytes and thyroid nodule cells during radioiodine therapy in patients with hyperthyroidism

Cited by 5 publications

References 17 publications

Micronucleus test and comet assay on mice fed over five generations a diet containing genetically modified triticale

Micronucleus test and comet assay on mice fed over five generations a diet containing genetically modified triticale

The assessment of genotoxic effects of wastewater from a fertilizer factory

Formation of carcinogenic chromosomal rearrangements in human thyroid cells after induction of double-strand DNA breaks by restriction endonucleases

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