Relationships among DNA hypomethylation, Cd, and Pb exposure and risk of cigarette smoking-related urothelial carcinoma

Chung, Chi Jung; Chang, Chao‐Hsiang; Liou, Saou‐Hsing; Liu, Chiu-Shong; Liu, Huei-Ju; Hsu, Li-Chuan; Chen, Jhih-Sheng; Lee, Hui‐Ling

doi:10.1016/j.taap.2016.12.016

Cited by 18 publications

(7 citation statements)

References 39 publications

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“…Research on patients all over the world indicate various harmful effect of cigarette smoking on a range of tissues and organs [32,[37][38][39]. The metal content of tobacco ranges from less than 1 µg/g (for Cd and Pb) to several hundred µg/g (as in the case of aluminum (Al), manganese (Mn), and barium (Ba)).…”

Section: Discussionmentioning

confidence: 99%

Analysis of Cadmium, Mercury, and Lead Concentrations in Erythrocytes of Renal Transplant Recipients from Northwestern Poland

Wilk

Romanowski

Wiszniewska

2021

Biology

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Cadmium (Cd), mercury (Hg), and lead (Pb) exhibit highly nephrotoxic properties, and their high concentrations can lead to renal failure. Much research has been conducted on the concentrations of heavy metals, microelements, and macroelements in the blood, but little is known about the concentration of Cd, Pb, and Hg in erythrocytes of renal recipients. The aim of this study is to determine the blood erythrocyte concentrations of toxic metals (Cd, Pb, and Hg) in renal transplant recipients (RTRs). Additionally, we analyzed the effect of selected biological and environmental factors, including the intake of various immunosuppressive drug regimens and smoking, on these xenobiotic concentrations. The material consisted of erythrocyte samples from 115 patients of the Department of Nephrology, Transplantology, and Internal Medicine at Independent Public Clinical Hospital No. 2, Pomeranian Medical University, Szczecin, in northwestern Poland. Cd, Hg, and Pb levels in the erythrocytes were quantified by inductively coupled mass spectroscopy (ICP-MS). Equal concentrations of Cd were found in erythrocytes of both female and male transplant recipients. The highest level of Hg was seen in women, and women overall had statistically higher concentrations of Pb than men. Comparison of metal concentrations between those over 50 years and those under it showed that Pb concentration was also significantly higher in renal transplant recipients over 50. Pb concentration was almost twice as high in RTRs who used tacrolimus with mycophenolate mofetil than in RTRs who used cyclosporine A with mycophenolate mofetil. The highest level of Cd was seen in smokers, who had 3.25 µg/L. This value was significantly higher than in ex-smokers (p = 0.001) and with RTRs who had never smoked. There were significantly higher levels of Pb in the erythrocytes of RTRs who were ex-smokers than in those who had never smoked. A statistically significant correlation was found between Cd and Pb concentrations. Additionally, we have noticed significant positive correlation between Pb and age (R = 0.37), gender (R = 0.24) and significant negative correlation of Pb with GFR (R = −0.33). We have also found significant positive correlation between Hg and age (R = 0.21). In summary, our data suggest that, smoking is associated with Pb and Cd concentrations, and gender, age change depending on Pb concentration in erythrocytes of RTRs. Additionally, this is the first research that suggests that immunosuppressive regimen, depending on type of immunosuppressive drugs combination affects Pb concentration in erythrocytes of RTRs. It seems to be crucial information for patients who use immunosuppressive drugs.

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Section: Discussionmentioning

confidence: 99%

Analysis of Cadmium, Mercury, and Lead Concentrations in Erythrocytes of Renal Transplant Recipients from Northwestern Poland

Wilk

Romanowski

Wiszniewska

2021

Biology

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“…The levels of 5mdC were quantified using high-performance liquid chromatography (Agilent 1260VL, Agilent Technology, Santa Clara, CA, USA) equipped with an API 3000™ triple quadrupole mass spectrometer (AB SCIEX, Concord, ON, Canada). The detailed protocol of the analysis has been described previously [ 18 , 19 ]. The 5mdC level present in the DNA sample was expressed as a percentage of the total cytosine content (methylated and non-methylated).…”

Section: Methodsmentioning

confidence: 99%

“…The 5mdC level present in the DNA sample was expressed as a percentage of the total cytosine content (methylated and non-methylated). The DNA methylation level was expressed as either (5mdC)/(5mdC + dC) without internal standard adjustments or (5mdC)/(dG) with adjustment to the respective 15 N-labeled internal standards, where dG is an internal standard that allows a simpler and accurate determination of dC methylation and avoids the use of expensive isotope-labeled internal standards [ 18 , 19 ]. Figure 1 displays the chromatogram of liquid chromatography-tandem mass spectrometry (LC-MS/MS) for detecting reference compounds of 5mdC.…”

Section: Methodsmentioning

confidence: 99%

“…The global loss of DNA methylation is a feature of cancer tissues [ 17 ]. Measuring the ratio of 5-methyl-2′deoxycytidine (5mdC) to 2′-deoxyguanine (dG) (5mdC (%)), assuming (dG) = (5mdC) + (2′-deoxycytidine, dC), provides an estimate of global DNA methylation levels [ 18 , 19 ]. At present, there are few studies using 5mdC (%) as a global DNA methylation marker to explore its relationship with cancer, especially RCC.…”

Section: Introductionmentioning

confidence: 99%

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Possible Combined Effects of Plasma Folate Levels, Global DNA Methylation, and Blood Cadmium Concentrations on Renal Cell Carcinoma

et al. 2023

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Epigenetic effects of environmental pollutants may be related to carcinogenesis. This study aimed to explore the association between the global DNA methylation marker: 5-methyl-2-deoxycytidine (5mdC) and renal cell carcinoma (RCC), and further investigated whether plasma folate and vitamin B12 levels and 5mdC modified the association between blood cadmium concentrations and RCC. We recruited 174 RCC patients and 673 non-RCC controls. Blood cadmium concentrations, plasma folate and vitamin B12 levels were measured. The amount of 5mdC in the DNA sample was expressed as percentages of the total cytosine content. An increase of 5mdC (%) and plasma folate and vitamin B12 levels were associated with decreasing odds ratio (OR) of RCC. Although plasma folate levels were not directly associated with 5mdC (%), a combined effect was observed with the odds of low plasma folate levels and low 5mdC (%) were greater among RCC patients compared to controls (OR (95% confidence interval, CI) = 11.86 (5.27–26.65)). Additionally, we observed that the odds of low plasma folate and high blood cadmium levels were greater among RCC patients than in controls (OR (95% CI): 8.15 (1.39–7.13)). This study provides suggestive evidence that plasma folate levels may modify the associations between 5mdC (%) or blood cadmium concentrations and RCC.

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“…Így például a daganatos betegségek kialakulásáért 90-95%ban környezeti tényezők tehetők felelőssé, és a genetika csak a daganatok 5-10%-ánál oka közvetlenül a betegség kialakulásának [2]. A dohányzás ismerten csökkenti a DNS metiláltsági állapotát: ez olyan szabályozási "jel" a génállományon, amely gátolja azon gének működését, melyekre aktuálisan nincs szükség, éppen ezért nem időszerű bekapcsolódásuk kisebb vagy nagyobb mértékben, de káros a szervezetre [3,4].…”

Section: öSszefoglaló Közleményunclassified

A DNS epigenetikai változásai és vizsgálati módszerei

Németh

Takács

Molnár

2022

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A humán DNS hordozza az emberi szervezet felépítéséhez és működéséhez szükséges összes információt, a legtöbb betegség kialakulása azonban elsődlegesen mégsem a genetikai anyagban rögzített információ változásának következménye. A mutációk például csak a daganatok 5–10%-ában közvetlen okai a betegség kialakulásának. A nukleotidszintű genetikai eltérések és strukturális variációk mellett a kromatin térbeli formaváltozása is hozzájárul a fenotípus kialakulásához a génátíródás, illetve a jelátviteli utak módosításán keresztül. Az emberi DNS epigenetikai szabályozás révén folyamatos átrendeződésen megy át. Ilyenkor a DNS nukleotidszekvenciája, információtartalma nem változik, hanem a szabályozó vagy kódoló régió válik aktívvá vagy inaktívvá a mindenkori fiziológiás szükségleteknek, életkori sajátosságoknak megfelelően. A DNS-nek ezt a szabályozott átrendeződését „remodeling”-nek hívjuk. Ennek célja, hogy a sejtekben mindig az aktuális működést biztosító fehérjéknek megfelelő génszakaszok íródjanak át. Ez a működés azonban az életkor előrehaladtával veszít hatékonyságából, és sok betegség kialakulása éppen az epigenetikai szabályozás egyensúlyának megbomlására vezethető vissza. Az epigenetikai változások vizsgálatára és mérésére több olyan régi és új elképzelés, illetve módszer van, melyek diagnosztikus alkalmazása segítséget adhat a betegségek korai előrejelzésében. Összefoglaló cikkünk az epigenetikai szabályozás sokrétűségét kívánja bemutatni, rávilágítva egyes központi molekulák, hormonok szerepére az öregedésben és az azzal összefüggő betegségek létrejöttében. Emellett a legújabb epigenetikai vizsgálómódszerek – úgymint a kromatin-immunprecipitáció (ChIP), a nyitott kromatinrészek feltérképezése, a metiláltsági szint vizsgálata – lényegét is ismerteti, melyek alkalmasak lehetnek a közeljövőben diagnosztikus módszerek kidolgozására is. Orv Hetil. 2022; 163(34): 1334–1344.

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Relationships among DNA hypomethylation, Cd, and Pb exposure and risk of cigarette smoking-related urothelial carcinoma

Cited by 18 publications

References 39 publications

Analysis of Cadmium, Mercury, and Lead Concentrations in Erythrocytes of Renal Transplant Recipients from Northwestern Poland

Analysis of Cadmium, Mercury, and Lead Concentrations in Erythrocytes of Renal Transplant Recipients from Northwestern Poland

Possible Combined Effects of Plasma Folate Levels, Global DNA Methylation, and Blood Cadmium Concentrations on Renal Cell Carcinoma

A DNS epigenetikai változásai és vizsgálati módszerei

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