DNA lesions and cytogenetic changes induced by N-nitrosomorpholine in HepG2, V79 and VH10 cells: the protective effects of Vitamins A, C and E

Robichová, Soňa; Slameñová, D; Chalupa, Ivan; Sebová, Lívia

doi:10.1016/j.mrgentox.2004.01.011

Cited by 28 publications

(6 citation statements)

References 38 publications

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“…Primary human VH10 fibroblasts (telomerase-immortalized cells) were obtained from the foreskin of a 10-year old boy [62]. The cells were cultured in DMEM (Dulbecco’s Modified Eagle’s Medium, Sigma-Aldrich, Stockholm, Sweden) supplemented with DBS (Bovine Calf Serum, HyClone, Thermo Fischer Scientific, Göteborg, Sweden) and PEST (Penicillin-streptomycin solution stabilized, Sigma-Aldrich).…”

Section: Methodsmentioning

confidence: 99%

Gamma-H2AX foci in cells exposed to a mixed beam of X-rays and alpha particles

et al. 2012

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BackgroundLittle is known about the cellular effects of exposure to mixed beams of high and low linear energy transfer radiation. So far, the effects of combined exposures have mainly been assessed with clonogenic survival or cytogenetic methods, and the results are contradictory. The gamma-H2AX assay has up to now not been applied in this context, and it is a promising tool for investigating the early cellular response to mixed beam irradiation.PurposeTo determine the dose response and repair kinetics of gamma-H2AX ionizing radiation-induced foci in VH10 human fibroblasts exposed to mixed beams of 241Am alpha particles and X-rays.ResultsVH10 human fibroblasts were irradiated with each radiation type individually or both in combination at 37°C. Foci were scored for repair kinetics 0.5, 1, 3 and 24 h after irradiation (one dose per irradiation type), and for dose response at the 1 h time point. The dose response effect of mixed beam was additive, and the relative biological effectiveness for alpha particles (as compared to X-rays) was of 0.76 ± 0.52 for the total number of foci, and 2.54 ± 1.11 for large foci. The repair kinetics for total number of foci in cells exposed to mixed beam irradiation was intermediate to that of cells exposed to alpha particles and X-rays. However, for mixed beam-irradiated cells the frequency and area of large foci were initially lower than predicted and increased during the first 3 hours of repair (while the predicted number and area did not).ConclusionsThe repair kinetics of large foci after mixed beam exposure was significantly different from predicted based on the effect of the single dose components. The formation of large foci was delayed and they did not reach their maximum area until 1 h after irradiation. We hypothesize that the presence of low X-ray-induced damage engages the DNA repair machinery leading to a delayed DNA damage response to the more complex DNA damage induced by alpha particles.

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Section: Methodsmentioning

confidence: 99%

Gamma-H2AX foci in cells exposed to a mixed beam of X-rays and alpha particles

et al. 2012

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“…The Panel noted that no neutralisation of the acidification of the culture medium was performed. Robichová et al (2004), found no induction of chromosomal aberrations in human Hep G2 cells in vitro with ascorbic acid at 0.5 mM for 1 hour without metabolic activation. Miller et al (1995) tested ascorbic acid in CHO cells without S9 with a 48-hour continuous treatment and with S9 (from livers of phenobarbital/β naphtoflavone induced-rats) with a 3-hour treatment followed by a 45-hour recovery period in only one culture/dose.…”

Section: Chromosomal Aberration Assaymentioning

confidence: 89%

Scientific Opinion on the re‐evaluation of ascorbic acid (E 300), sodium ascorbate (E 301) and calcium ascorbate (E 302) as food additives

2015

EFS2

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The EFSA Panel on Food additives and Nutrient Sources added to Food (ANS Panel) provides a scientific opinion re‐evaluating the safety of ascorbic acid (E 300), sodium ascorbate (E 301) and calcium ascorbate (E 302) as food additives. The use of ascorbic acid and its salts as food additives was evaluated by the Joint FAO/WHO Expert Committee on Food Additives and by the Scientific Committee on Food. Ascorbic acid is absorbed from the intestine by a sodium‐dependent active transport process and, at low doses, the absorption is almost complete until a saturation point, after which increasing amounts of unabsorbed substance are excreted. Ascorbic acid and its salts have very low acute toxicities, and short‐term tests in animals showed little effect, and even so only at high doses. The Panel concluded that there is no genotoxicity concern for ascorbic acid, sodium ascorbate or calcium ascorbate. Long‐term carcinogenicity tests with ascorbic acid did not show any chronic toxicity, even at high doses, and also showed no signs of carcinogenicity. Prenatal developmental studies did not show adverse developmental effects. The Panel estimated the combined exposure to ascorbic acid (E 300), calcium ascorbate (E 301) and sodium ascorbate (E 302). The Panel concluded that, given the fact that adequate data on exposure and toxicity were available and no adverse effects were reported in animal studies, there is no safety concern for the use of ascorbic acid (E 300), sodium ascorbate (E 301) and calcium ascorbate (E 302) as food additives at the reported uses and use levels and there is no need for a numerical ADI for ascorbic acid and its salts.

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“…It is well known that in the presence of nitrite, MOR can be converted to NMOR both in vitro and in vivo. NMOR is widely used as hepatocarcinogen in experimental models and might induce DNA damage via formation of ROS/RNS (Robichová et al, 2004;Erkekoglu and Baydar, 2010). In the current study, TPO, LPO, NO and O 2 -were significantly increased in the lung and colon tissues of rats treated with nitrite combined with MOR for 15 weeks.…”

Section: Discussionmentioning

confidence: 99%

“…NMOR induce DNA damage via at least two different pathways: directly via formation of NO . and indirectly through N-hydroxylamines generated by drugmetabolizing enzymes (Robichová et al, 2004). Moreover, ROS/RNS are potent intrinsic stimuli for apoptosis that modulate apoptosis when cell are under stress by mitochondrial damage (Reed, 1997).…”

Section: Discussionmentioning

confidence: 99%

The protective role of 3-aminothiazolo[3-2a]benzimadzole-2-carbonitrile against lung and colon injury induced by nitrosomorpholine in adult male albino rat

Omar¹,

Abd-Allah²,

El-Din³

et al. 2013

J. Toxicol. Environ. Health Sci.

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Nitrites and morpholine are ubiquitous environmental contaminants found in drinking water and food. NMOR can be formed endogenously from nitrite and morpholine. Increased levels of reactive oxygen species/ reactive nitrite species (ROS/RNS) are involved in the mechanism of NMOR toxicity. Certain antimicrobial, antifungal and antioxidant potential were observed in heterocyclic benzimidazole derivatives and dimethyl sulfoxide (DMSO). This study was designed to evaluate the biological potential of 3-aminothiazolo[3-2a]benzimadzole-2-carbonitrile in the protection of lung and colon tissues against the increased levels of ROS/RNS that are induced by administration of nitrite and morpholine in drinking water for 15 weeks. Forty adult male rats were categorized into 4 groups, 10 rats each. The results showed a significant increase in NO, lipid peroxidation (LPO), total peroxides (TPO), superoxide anion (O 2 -) and DNA fragmentation in lung and colon tissues of rats treated with nitrite and morpholine compared to the control group. Moreover, histological observation of the lung and colon tissues showed cell necrosis, increase in the leukocyte infiltration and blood vessel congestion. Immunostaining for inducible nitric oxide synthase (iNOS) showed positive reaction for lung and colon tissues. After the co-treatment of rats with DEMSO and 3-aminothiazolo[3-2a]benzimadzole-2-carbonitrile, all the previous biochemical changes were reduced in addition to the relative improvement in the morphological changes of both lung and colon. In conclusion, the injury in lung and colon tissues induced by nitrite and morpholine may return to the increased production of ROS and to the alterations in the levels of antioxidants. Co-treatment of rats with 3-aminothiazolo[3-2a]benzimadzole-2-carbonitrile and DMSO may protect them against nitrite and morpholine toxicity.

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DNA lesions and cytogenetic changes induced by N-nitrosomorpholine in HepG2, V79 and VH10 cells: the protective effects of Vitamins A, C and E

Cited by 28 publications

References 38 publications

Gamma-H2AX foci in cells exposed to a mixed beam of X-rays and alpha particles

Gamma-H2AX foci in cells exposed to a mixed beam of X-rays and alpha particles

Scientific Opinion on the re‐evaluation of ascorbic acid (E 300), sodium ascorbate (E 301) and calcium ascorbate (E 302) as food additives

The protective role of 3-aminothiazolo[3-2a]benzimadzole-2-carbonitrile against lung and colon injury induced by nitrosomorpholine in adult male albino rat

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