Immunohistochemical Evidence of High Concentrations of Metallothionein in Pancreatic Hepatocytes Induced by Cadmium in Rats

Waalkes, Michael P.; Cherian, M. George; Ward, Jerrold M.; Goyer, Robert A.

doi:10.1177/019262339202000302

Cited by 17 publications

(7 citation statements)

References 21 publications

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“…Cadmium may have influence on several biological systems by replacing zinc because they belong to the same column in the periodic table and share many physical and chemical properties (Schwartz and Reis 2000). Second, cadmium is known as one of the most potent agents to cause transdifferentiation of the pancreas (Waalkes et al 1992). Cadmium may put cells at a higher risk of neoplasia since transdifferentiation involves cellular dedifferentiation, proliferation, and redifferentiation (Yuan et al 1996).…”

Section: Discussionmentioning

confidence: 99%

Cadmium exposure and risk of pancreatic cancer: a meta-analysis of prospective cohort studies and case–control studies among individuals without occupational exposure history

Chen

Xun

Nishijo

et al. 2015

Environ Sci Pollut Res

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Pancreatic cancer is one of the most deadly types of cancer for both genders. Classified as a human carcinogen, cadmium has been related to diverse cancers. However, the association between cadmium exposure and the risk of pancreatic cancer is still unclear. We quantitatively reviewed the observational studies on the association of cadmium exposure with pancreatic cancer risk among individuals without occupational exposure history published through July 2014 in PubMed by using a fixed–effects model. Four prospective cohort studies (112,934 participants with 335 events) and two case-control studies (177 cases and 539 controls) were identified. The summarized relative risk (RR) with a 95% confidence interval (CI) was 2.05 (95% CI=1.58 – 2.66), comparing the highest to the lowest category of cadmium exposure. This positive association persisted in men (RR=1.78; 95% CI=1.04 – 3.05), but not in women (RR=1.02; 95% CI=0.63 – 1.65). Further research is needed to provide more solid evidence on the association of cadmium exposure with pancreatic cancer risk and to elucidate the underlying biological mechanism of the potential gender difference.

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Section: Discussionmentioning

confidence: 99%

Cadmium exposure and risk of pancreatic cancer: a meta-analysis of prospective cohort studies and case–control studies among individuals without occupational exposure history

Chen

Xun

Nishijo

et al. 2015

Environ Sci Pollut Res

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“…Cadmium is a well established carcinogen that acts on different steps of carcinogenesis, inhibiting DNA repair, and causing genomic instability 16–18. Furthermore, it causes transdifferentiation of pancreatic cells, inhibits DNA repair, and induces or regulates the activity of several oncogenes or tumour-suppressor proteins that are expressed in human pancreatic cancer 5 19 20…”

Section: Discussionmentioning

confidence: 99%

Pancreatic cancer risk and levels of trace elements

Amaral

Porta

Silverman

et al. 2011

Gut

102

112

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Background and aims Knowledge on the etiology of exocrine pancreatic cancer (EPC) is scant. The best established risk factor for EPC is tobacco smoking. Among other carcinogens, tobacco contains cadmium, a metal previously associated with an increased risk of EPC. We evaluated the association between concentrations of trace elements in toenails and EPC risk. Methods The study included 118 EPC cases and 399 hospital controls from Eastern Spain. Levels of twelve trace elements were determined in toenail samples by inductively coupled plasma - mass spectrometry. Odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for potential confounders, were calculated using logistic regression. Results Significantly increased risks of EPC were observed among subjects whose concentrations of cadmium (OR=3.58, 95%CI 1.86–6·88; Ptrend=5×10−6), arsenic (OR=2.02, 95%CI 1.08–3.78; Ptrend=0.009), and lead (OR=6.26, 95%CI 2.71–14.47; Ptrend=3×10−5) were in the highest quartile. High concentrations of selenium (OR=0.05, 95%CI 0.02–0.15; Ptrend=8×10−11) and nickel (OR=0.27, 95%CI 0.12–0.59; Ptrend=2×10−4) were inversely associated with risk of EPC. Conclusion We report novel associations of lead, nickel, and selenium toenail concentrations with pancreas cancer risk. Furthermore, results confirm previous associations with cadmium and arsenic. These novel findings, if replicated in independent studies, would point to an important role of trace elements in pancreatic carcinogenesis.

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“…The structure of MT and Cd binding sites were described in detail by Cols et al (1997) and . Metallothionein is synthesized and detected in many tissues of animals and plays an important role in the transport of metals and the detoxification process (Chan and Cherian, 1992;Klaassen and LehmanMckeeman, 1989;Waalkes et al, 1992a). MT is localized in cytoplasm.…”

Section: Role Of Metallothionein and Glutathione In Cadmium Accumulatmentioning

confidence: 99%

“…Cadmium may produce histological changes in the kidneys, liver (Goyer et al, 1989;Suzuki et al, 1983), the gastrointestinal tract, testes, heart, blood vessels, bone marrow, and pancreas (Domino, 1994;Selypes et al, 1992;Ś wiergosz et al, 1998;Waalkes et al, 1992aWaalkes et al, , 1994. Sub-lethal effects such as reduced growth and anemia may also occur (Pleasants et al,Fig.…”

Section: Tissue Damagementioning

confidence: 99%

Cadmium distribution and toxicity in tissues of small rodents

Świergosz-Kowalewska

2001

Microscopy Res & Technique

110

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The aim of the present paper is to discuss the accumulation and distribution of cadmium (Cd) in the various tissues of animals, the interactions of cadmium with other elements, and the damage to tissues caused by this metal. Cadmium is not physiologically or biochemically essential to an organism. It is absorbed via the gastrointestinal tract and lungs and accumulated in various tissues, mainly the kidneys and liver. The distribution of cadmium between various tissues depends on many endogenous and exogenous factors. Cadmium is bound to a low-molecular-weight protein, metallothionein (MT), and to high-molecular-weight proteins. This metal has a great affinity to thiol groups. Cadmium binds also to O- and N-containing ligands. The distribution of cadmium between organs differs markedly depending on the chemical form of administered Cd and the duration of exposure. Acute exposure results in a different distribution pattern throughout the body than does chronic exposure. Long-term exposure to high doses of cadmium may cause biochemical and functional changes in some critical organs. Cadmium can influence the absorption and distribution of essential elements and can replace them in enzymes. Metallothionein and glutathione play important roles in the transport of metals and in detoxification processes. Reported findings are mainly the results of experiments on laboratory animals. The lack of data concerning the localization of cadmium in various tissues of wild species is noticeable and there is a great need for such data.

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Immunohistochemical Evidence of High Concentrations of Metallothionein in Pancreatic Hepatocytes Induced by Cadmium in Rats

Cited by 17 publications

References 21 publications

Cadmium exposure and risk of pancreatic cancer: a meta-analysis of prospective cohort studies and case–control studies among individuals without occupational exposure history

Cadmium exposure and risk of pancreatic cancer: a meta-analysis of prospective cohort studies and case–control studies among individuals without occupational exposure history

Pancreatic cancer risk and levels of trace elements

Cadmium distribution and toxicity in tissues of small rodents

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