Cadmium chloride-induced dysplastic changes in the ventral rat prostate: An immunohistochemical and quantitative study

Martín, José Jesús Martín; Martı́n, Rocı́o; Codesal, J.; Fraile, Benito; Paniagua, Ricardo; Santamarı́a, Luis

doi:10.1002/1097-0045(200101)46:1<11::aid-pros1003>3.0.co;2-k

Cited by 30 publications

(18 citation statements)

References 28 publications

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“…There are few previous studies exploring chronic exposure to orally administered cadmium (Martin et al 2001;Alvarez et al 2004). For this reason, in the present work, we designed a model to mimic an environmental oral exposure to cadmium in order to find out its effect on the prostate, focusing our attention especially on ultrastructure and lipid metabolism.…”

Section: Introductionmentioning

confidence: 99%

Effects of chronic exposure to cadmium on prostate lipids and morphology

et al. 2006

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Cadmium is an environmental toxic metal implicated in human prostate carcinogenesis. The mechanism of its toxicity is not fully understood. Previously, we showed that cadmium exposure induces oxidative stress, especially lipid peroxidation. This study evaluates the effect of chronic exposure to 0.886 mM of cadmium (Cd) per liter in the drinking water on prostate lipid content and metabolism in Wistar rats. We determined the lipid profile and measured the expression of lipogenic enzymes: FAS, GPAT, LPL, DGAT-1, DGAT-2, ACO, CPT-1 and CT, and of certain factors involved in lipid regulation and fatty acid transporters: FAT/CD36, E-FABP, SREBP-2, PPAR-gamma and PPAR-alpha by RT-PCR. Ultrastructure was analyzed by electron microscopy and, as prostate is an androgen controlled gland, AR expression was measured by RT-PCR and Western blot. Cd altered the prostatic lipid profile. Triglycerides (TG) and esterified cholesterol (EC) decreased, free cholesterol (FC) and phospholipids (PL) increased and total cholesterol (TC) did not change. FAS, MDH and IDH activities did not vary but G6PDH decreased significantly in Cd group. Regarding TG synthesis, DGAT-1 decreased while GPAT increased and FAS, LPL and DGAT-2 remained unchanged. Regarding beta oxidation, CPT-1 increased while ACO expression decreased in Cd group. In the PL pathway, CT expression was increased. All these results would justify the decrease of TG in Cd group when compared to control. In the cholesterol metabolic pathway, HMGCoAR and SREBP-2 increased. PPAR-alpha increased but PPAR-gamma did not change. Regarding fatty acid transporters, FAT/CD36 decreased, while E-FABP increased. AR mRNA and protein expression decreased. Ultrastructural analysis showed a decrease in lipid droplets and signs of cellular damage in the Cd group. Cadmium exposure induces important changes in prostatic lipid profile and metabolism, confirmed by the morphology analyses, which also showed signs of cellular damage. These results could be important to further understanding the complex mechanism of cadmium toxicity in prostate and in the development of better treatments for people and animals exposed to the heavy metal.

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Section: Introductionmentioning

confidence: 99%

Effects of chronic exposure to cadmium on prostate lipids and morphology

et al. 2006

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“…Waalkes et al (1989) [35] demonstrated a dose-response relation in a rodent model when tumors were induced by injecting cadmium subcutaneously. Our experimental model based on the administration of low doses of cadmium chloride induces higher incidence of prostate carcinogenesis in Sprague-Dawley rats in a manner similar to that of humans [6]–[8], [27].…”

Section: Discussionmentioning

confidence: 94%

“…The percentages of LPA-1–immunostained nuclei (LPA-1 labeling index, LI LPA1 ), PCNA-immunopositive nuclei (PCNA labeling index, LI PCNA ), labeled apoptotic nuclei (apoptotic labeling index, LI APO ), ubiquitin-immunostained nuclei (UBI labeling index, LI UBI ), and p53-immunostained nuclei (p53 labeling index, LI p53 ) were calculated in each selected section for control rats, nondysplastic acini of cadmium-treated (Cd-treated) rats, and dysplastic acini of Cd-treated animals, using the following formula: number of labeled nuclei×100/total number (labeled + unlabeled) of nuclei [6], [8], [27], [29].…”

Section: Methodsmentioning

confidence: 99%

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Expression of Lysophosphatidic Acid Receptor 1 and Relation with Cell Proliferation, Apoptosis, and Angiogenesis on Preneoplastic Changes Induced by Cadmium Chloride in the Rat Ventral Prostate

et al. 2013

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BackgroundLysophosphatidic acid (LPA) is a phospholipid growth factor involved in cell proliferation, differentiation, migration, inflammation, angiogenesis, wound healing, cancer invasion, and survival. This study was directed to evaluate the immunoexpression of LPA-1, cell proliferation, apoptosis, and angiogenesis markers in preneoplastic lesions induced with cadmium chloride in rat prostate.MethodsThe following parameters were calculated in ventral prostate of normal rats and rats that received Cd in drinking water during 24 months: percentages of cells immunoreactive to LPA-1 (LILPA1), PCNA (LIPCNA), MCM7 (LIMCM7), ubiquitin (LIUBI), apoptotic cells (LIAPO), and p53 (LIp53); volume fraction of Bcl-2 (VFBcl-2); and length of microvessels per unit of volume (LVMV/mm3). Data were analyzed using Student's t-test and Pearson correlation test.ResultsThe LILPA1 in dysplastic lesions and normal epithelium of Cd-treated rats was significantly higher than those in the control group. Markers of proliferation were significantly increased in dysplastic lesions, whereas some apoptotic markers were significantly decreased. No significant differences between groups were found in VFBcl-2. Dysplastic lesions showed a significant increase of LIp53. The length of microvessels per unit of volume was elevated in dysplastic acini. Statistically significant correlations were found only between LILPA1 and LIUBI.ConclusionsOur results suggest that LPA-1 might be implicated in dysplastic lesions induced by cadmium chloride development. More studies are needed to confirm its potential contribution to the disease.

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“…The cells transformed by cadmium demonstrate morphological alterations, anchorage-independent growth in soft agar, and formation of tumors when transplanted into SCID mice [6]. In addition, cadmium chloride has been shown to produce premalignant and/or invasive epithelial lesions in the rat ventral prostate when administered in drinking water [7-9]. Interestingly, patients with prostate cancer appear to have higher levels of cadmium both in the circulation and in prostatic tissues [10].…”

Section: Introductionmentioning

confidence: 99%

Cadmium down-regulates expression of XIAP at the post-transcriptional level in prostate cancer cells through an NF-κB-independent, proteasome-mediated mechanism

et al. 2010

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BackgroundCadmium has been classified as a human carcinogen, affecting health through occupational and environmental exposure. Cadmium has a long biological half-life (>25 years), due to the flat kinetics of its excretion. The prostate is one of the organs with highest levels of cadmium accumulation. Importantly, patients with prostate cancer appear to have higher levels of cadmium both in the circulation and in prostatic tissues.ResultsIn the current report, we demonstrate for the first time that cadmium down-regulates expression of the X-linked inhibitor of apoptosis protein (XIAP) in prostate cancer cells. Cadmium-mediated XIAP depletion occurs at the post-transcriptional level via an NF-κB-independent, proteasome-mediated mechanism and coincides with an increased sensitivity of prostate cancer cells to TNF-α-mediated apoptosis. Prolonged treatment with cadmium results in selection of prostate cancer cells with apoptosis-resistant phenotype. Development of apoptosis-resistance coincides with restoration of XIAP expression in cadmium-selected PC-3 cells.ConclusionsSelection of cadmium-resistant cells could represent an adaptive survival mechanism that may contribute to progression of prostatic malignancies.

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Cadmium chloride-induced dysplastic changes in the ventral rat prostate: An immunohistochemical and quantitative study

Cited by 30 publications

References 28 publications

Effects of chronic exposure to cadmium on prostate lipids and morphology

Effects of chronic exposure to cadmium on prostate lipids and morphology

Expression of Lysophosphatidic Acid Receptor 1 and Relation with Cell Proliferation, Apoptosis, and Angiogenesis on Preneoplastic Changes Induced by Cadmium Chloride in the Rat Ventral Prostate

Cadmium down-regulates expression of XIAP at the post-transcriptional level in prostate cancer cells through an NF-κB-independent, proteasome-mediated mechanism

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