Role of Oxidative Stress in Transformation Induced by Metal Mixture

Škandík, Martin; Rojas, Emilio; Valverde, Mahara

doi:10.1155/2011/935160

Cited by 11 publications

(8 citation statements)

References 39 publications

(58 reference statements)

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“…Finally, we needed to elucidate whether the effects of miR-222 are relevant to the cellular transformation endpoint assessed by morphological changes and foci formation in Balb/c 3T3 model [39,48,57], we observed that the use of the pre-miR-222 as an initiator (combined with the known promoter TPA [56] accelerates transformation and generates foci on day 13 " Fig 5". Furthermore, pre-miR-222 also produce more foci number when it is used as a initiator and promoter stimulus, but not when is used only as a promoter stimulus (along with the known initiator agent MNNG [58,59]), confirming the cellular consequences of elevated levels of this miRNA.…”

Section: Discussionmentioning

confidence: 99%

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Post-transcriptional regulation of Rad51c by miR-222 contributes cellular transformation

et al. 2020

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DNA repair inhibition has been described as an essential event leading to the initiation of carcinogenesis. In a previous study, we observed that the exposure to metal mixture induces changes in the miR-nome of the cells that was correlated with the sub-expression of mRNA involved in processes and diseases associated with metal exposure. From this analysis, one of the miRNAs that shows changes in its expression is miR-222, which is overexpressed in various cancers associated with exposure to metals. In silico studies showed that a possible target for the microRNA-222 could be Rad 51c, a gene involved in the doublestranded DNA repair. We could appreciate that up-regulation of miR-222 reduces the expression both gene and as a protein expression of Rad51c by RT-PCR and immunoblot, respectively. A luciferase assay was performed to validate Rad51c as miR-222 target. Neutral comet assay was performed in order to evaluate DNA double-strand breaks under experimental conditions. Here, we demonstrate that miR-222 up-regulation, directly regulates Rad51c expression negatively, and impairs homologous recombination of doublestrand break DNA repair during the initiation stage of cell transformation. This inhibition triggers morphological transformation in a two-stage Balb/c 3T3 cell assay, suggesting that this small RNA acts as an initiator of the carcinogenesis process.

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Section: Discussionmentioning

confidence: 99%

“…The two-stage Balb/c 3T3 cell assay was performed as described previously with slight modifications [48,49]. The transformation protocol consisted of 13 days, divided in two phases: initiation between days 1 to 7 and promotion between days 7 to 13.…”

Section: Two-stage Balb/c 3t3 Cell Assaymentioning

confidence: 99%

Post-transcriptional regulation of Rad51c by miR-222 contributes cellular transformation

et al. 2020

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“…Decreased body weight gain in exposed animals relative to control indicated the growth retarding effect of the mixture of these three heavy metals on female albino rats. Reports suggested reduction in food and water intake might contribute to decrease in body weight gain in exposed animal 25 . The reduction of weight of reproductive organs ovary and uterus was indicative of toxic effect of the metal mixture on reproductive system of female rats treated with metal mixture.…”

Section: Discussionmentioning

confidence: 99%

Effect of Exposure to Mixture of Heavy Metals Arsenic, Cadmium and Lead on Reproductive Function and Oxidative Stress in Female Rats

Choudhuri

Bhattacharjee

2017

IJTPR

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Background : Toxicological consequences arising from exposure to mixtures of heavy metals especially at low, chronic and environmentally relevant doses are poorly recognised. In the present study, we evaluated effects of chronic exposure to combinations of three metals arsenic (As), cadmium (Cd) and lead (Pb) present frequently in drinking water on reproductive function and oxidative damage caused to reproductive organs of female rats. Method : Female rats were exposed to mixture of metals (As, Cdand Pb) for 90 consecutive days. The gain in body weight and weight of reproductive organs were recorded following autopsy on 91 stday. The oestrus cycle were monitored during entire treatment period. Numbers of corpora lutea, implantation sites, live fetus and survival of the fetus were evaluated in rats mated successfully with untreated male after completion of their respective treatment. Ovarian cholesterol, protein, ascorbic acid and enzyme Δ 5 -3β HSD levels were estimated. Serum levels of steroid hormones oestrogen and progesterone were estimated. Histopathological picture of both ovary and uterus were assessed. Levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidise (GPX) activity, amount of reduced glutathione (GSH) and malondyaldehyde (MDA) in blood, ovary and uterus were measured as biomarkers of oxidative stress. Results : The treated rats showed reduced body weight gain and reduction in the weight of ovary and uterus. Oestrus cycle was disrupted with continuous diestrous in treated animals. Number of corpora lutea, implantation sites and live fetus and the survival of fetus evaluate were reduced significantly in treated groups. The levels of ovarian cholesterol and ascorbic acid increased in treated rats with decrease Δ5 -3β HSD level. There was reduction in serum level of both the ovarian steroid hormones oestrogen and progesterone. The protein levels did not differ between the groups. There was a significant increase in levels of MDA and decrease in levels of all the antioxidant enzymes in treated group. Conclusion : The results revealed there was disruption to reproductive functions with decrease in stereoidogenic activity and associated oxidative stress in female rats treated with combination of mixture of metals (Cd, As and Pb) at low dose for 90 consecutive days.

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“…Low arsenic concentrations alter glucocorticoid signaling [135], function in oxidative stress [136], contribute to hypertension [137] and increase the risk of birth defects [138]. Arsenic also can induce cancer [137] and contributes to increased cardiovascular disease [139], skin lesions, diabetes, reproductive toxicity, neurologic disease and neurobehavioral disorders.…”

Section: Some Environmental Causes Of Epigenetic Changesmentioning

confidence: 99%

“…Sexual dimorphism may exist in the interaction between arsenic and dietary methyl donors [175]. Arsenic, other heavy metals and organic toxins may affect the epigenome via cellular responses to oxidative stress involving insulin signaling PPARγ-dependent pathways [136,139]. …”

Section: Some Environmental Causes Of Epigenetic Changesmentioning

confidence: 99%

The Epigenetic Lorax: Gene–Environment Interactions in Human Health

2012

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Over the last decade, we have witnessed an explosion of information on genetic factors underlying common human diseases and disorders. This ‘human genomics’ information revolution has occurred as a backdrop to a rapid increase in the rates of many human disorders and diseases. For example, obesity, Type 2 diabetes, asthma, autism spectrum disorder and attention deficit hyperactivity disorder have increased at rates that cannot be due to changes in the genetic structure of the population, and are difficult to ascribe to changes in diagnostic criteria or ascertainment. A likely cause of the increased incidence of these disorders is increased exposure to environmental factors that modify gene function. Many environmental factors that have epidemiological association with common human disorders are likely to exert their effects through epigenetic alterations. This general mechanism of gene–environment interaction poses special challenges for individuals, educators, scientists and public policy makers in defining, monitoring and mitigating exposures.

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Role of Oxidative Stress in Transformation Induced by Metal Mixture

Cited by 11 publications

References 39 publications

Post-transcriptional regulation of Rad51c by miR-222 contributes cellular transformation

Post-transcriptional regulation of Rad51c by miR-222 contributes cellular transformation

Effect of Exposure to Mixture of Heavy Metals Arsenic, Cadmium and Lead on Reproductive Function and Oxidative Stress in Female Rats

The Epigenetic Lorax: Gene–Environment Interactions in Human Health

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