Assessment of Proliferative Activity by AgNOR and PCNA in Prostatic Tissues of Ram Lambs Implanted with Zeranol

Gulbahar, MY; Yüksel, Hayati; Güvenç, Tolga; Okut, Hayrettin

doi:10.1111/j.1439-0531.2005.00604.x

Cited by 7 publications

(4 citation statements)

References 31 publications

(64 reference statements)

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“…Marked differences were found in the epithelial kinetics of the control groups at different ages as older rats showed fewer AR‐positive cells and lower cell proliferation rates. Cell proliferation was determined here by immunocytochemistry for PCNA protein and is highly expressed in the nuclei during the S‐phase of cell cycle (Bravo & Macdonald‐Bravo 1987; Kelman 1997; Gulbahar et al. 2005).…”

Section: Discussionmentioning

confidence: 99%

Proliferation and apoptotic rates and increased frequency of p63‐positive cells in the prostate acinar epithelium of alloxan‐induced diabetic rats

Arcolino

Ribeiro

Gobbo

et al. 2010

Int J Experimental Path

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The effects of experimental type 1 diabetes were investigated in the acinar epithelium of rat ventral prostate, focusing on the rates of cell proliferation and the frequency of apoptosis and p63-positive cells. Type 1 diabetes was induced in adult male Wistar rats by a single alloxan administration (42 mg/kg b.w.) and its effects were analysed for 1 week and 3 months after the establishment of the disease. A group of diabetic rats was treated daily with 5 IU of insulin during 1 week after diabetes had been diagnosed. Immunocytochemical methods for the localization of cell proliferation antigen (PCNA), androgen receptor (AR) and p63 protein were carried out, and apoptotic cells were identified by TUNEL essay. In diabetic rats, testosterone levels reduced drastically after 1 week and in a lower degree after 3 months. In short-term diabetic rats, cell proliferation decreased, and in medium-term, epithelial apoptotic rates increased. In both periods after the onset of diabetes, the frequency of p63-positive cells doubled. Insulin treatment was effective in preventing testosterone decrease, p63-positive cell increase and apoptotic rates, but did not interfere in cell proliferation. This investigation shows that, soon after diabetes onset, there are important modifications in cell proliferation within the acinar prostatic epithelium, and in longer term, there is a marked impact on kinetics of differentiation and cell death, which may initially be attributable to an androgenic fall, but is probably also because of other factors related to diabetes, as changes are considerably different from those resulting from castration.

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Section: Discussionmentioning

confidence: 99%

Proliferation and apoptotic rates and increased frequency of p63‐positive cells in the prostate acinar epithelium of alloxan‐induced diabetic rats

Arcolino

Ribeiro

Gobbo

et al. 2010

Int J Experimental Path

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“…Zeranol did not significantly affect mammary carcinogenesis by week 37. In contrast, zeranol exposure has been associated with precancerous changes in the liver of the Armenian hamster [48], which is especially sensitive to estrogen, and in the prostate of the Akkaraman lamb [49].…”

Section: Zeranolmentioning

confidence: 98%

Hormone Use in Food Animal Production: Assessing Potential Dietary Exposures and Breast Cancer Risk

Nachman

Smith

2015

Curr Envir Health Rpt

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In recent years, increasing attention has been paid to the role of hormones in breast cancer etiology, following reports that heightened levels of endogenous hormones and exposure to exogenous hormones and other endocrinedisrupting chemicals through food and the environment are associated with increased breast cancer risk. Seven hormone drugs (testosterone propionate, trenbolone acetate, estradiol, zeranol, progesterone, melengestrol acetate, and bovine somatotropin) are approved by the U.S. Food and Drug Administration for use in food animals. There is concern that these drugs or their biologically active metabolites may accumulate in edible tissues, potentially increasing the risk of exposure for consumers. To date, the potential for human exposure to residues of these compounds in animal products, as well as the risks that may result from this exposure, is poorly understood. In this paper, we discuss the existing scientific evidence examining the toxicological significance of exposure to hormones used in food animal production in relation to breast cancer risk. Through a discussion of U.S. federal regulatory programs and the primary literature, we interpret the state of surveillance for residues of hormone drugs in animal products and discuss trends in meat consumption in relation to the potential for hormone exposure. Given the lack of chronic bioassays of oral toxicity of the seven hormone compounds in the public literature and the limitations of existing residue surveillance programs, it is not currently possible to provide a quantitative characterization of risks that result from the use of hormonal drugs in food animal production, complicating our understanding of the role of dietary hormone exposure in the population burden of breast cancer.

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“…In another study devoted to the effects of zeranol on prostate tissue (Gulbahar et al, 2005), 24 Akkaraman lambs were implanted with increasing zeranol doses, of 12 mg (n = 8), 24 mg (n = 8) and 96 mg (n = 8), with eight lambs serving as controls. After 33 days, the prostate tissues of the lambs were stained using AgNOR (silver-stained nucleolar organizer regions) and PCNA (proliferating cell nuclear antigen) techniques.…”

Section: In Vivo Studiesmentioning

confidence: 99%

“…No morphological changes of the uterus, vagina and mammary tissue were observed. The zeranol doses used in these rodent and pig studies were, however, considerably higher (10 2 -10 4 fold) than the estimated concentrations which might be found as residues in tissues of zeranol-treated cattle.In another study devoted to the effects of zeranol on prostate tissue (Gulbahar et al, 2005), 24 Akkaraman lambs were implanted with increasing zeranol doses, of 12 mg (n = 8), 24 mg (n = 8) and 96 mg (n = 8), with eight lambs serving as controls. After 33 days, the prostate tissues of the 6 Ralgro is one of the commercial products containing zeranol in a slow release formulation.…”

mentioning

confidence: 99%

Opinion of the Scientific Panel on contaminants in the food chain (CONTAM) related to hormone residues in bovine meat and meat products

2007

EFSA Journal

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SUMMARYIn line with the obligations as defined in Article 11a of Directive 96/22/EC as amended by Directive 2003/74/EC the Commission asked EFSA to examine new data on substances and products thereof with hormonal activity which may be used legally in Third Countries for growth promoting purposes in bovine meat production. The substances under consideration are the naturally occurring steroids, testosterone and progesterone, as well as the synthetic compounds trenbolone acetate, which has demonstrated affinity to androgen receptors, zeranol, which has a high affinity for oestrogen receptors, and melengestrol acetate, which resembles progestins. In accordance with the mandate, the Panel on Contaminants in the Food Chain reviewed the scientific literature that became available in the period between 2002 and the first few months of 2007, until drafting of the present Opinion. The Panel noted that the understanding of the complex mechanisms of action of steroid hormones is still a matter of scientific research and new insights into the complex genomic and non-genomic regulatory mechanisms controlling hormonal homeostasis in different phases of life are still emerging.The Panel noted the availability of advanced methods of analysis with high sensitivity and reproducibility, allowing the measurement of residues of natural and synthetic hormones in animal tissues. However, no surveillance studies quantifying the amount and nature of residues in edible tissues of cattle treated with growth promoting hormones under practical conditions have been conducted in countries that have licensed the use of growth promoting hormones. At present, epidemiological data provide convincing evidence for an association between the amount of red meat consumed and certain forms of hormone-dependent cancers. Whether or not hormone residues in meat contribute to this risk is currently unknown.The CONTAM Panel concluded that the new data that are publicly available do not provide quantitative information that would be informative for risk characterisation and therefore do not call for a revision of the previous assessments of the Scientific Committee on Veterinary Measures relating to Public Health (SCVPH) (EC, 1999(EC, , 2000(EC, , 2002.KEYWORDS: growth promoting hormones, testosterone, progesterone, trenbolone acetate, zeranol, melengestrol acetate. TERMS OF REFERENCEThe Commission asks EFSA to examine new data on substances and products thereof with hormonal activity, which may be used legally in Third Countries for growth promoting purposes in beef cattle, e.g. testosterone, progesterone, trenbolone acetate, zeranol and melengestrol acetate, that became publicly available after the last assessment of potential risks to human health from hormone residues in bovine meat and meat products of the Scientific Committee on Veterinary Measures relating to Public Health (SCVPH) in 2002 and to indicate whether such new data would call for a revision of the previous SCVPH reports (EC, 1999(EC, , 2000(EC, , 2002.1 OJ L 125, 23.5.1996, p. 3-9....

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Assessment of Proliferative Activity by AgNOR and PCNA in Prostatic Tissues of Ram Lambs Implanted with Zeranol

Cited by 7 publications

References 31 publications

Proliferation and apoptotic rates and increased frequency of p63‐positive cells in the prostate acinar epithelium of alloxan‐induced diabetic rats

Proliferation and apoptotic rates and increased frequency of p63‐positive cells in the prostate acinar epithelium of alloxan‐induced diabetic rats

Hormone Use in Food Animal Production: Assessing Potential Dietary Exposures and Breast Cancer Risk

Opinion of the Scientific Panel on contaminants in the food chain (CONTAM) related to hormone residues in bovine meat and meat products

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