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Estradiol valerate-induced atypical endometrial hyperplasia in experimental polycystic ovary
S150
Abstracts / Toxicology Letters 189S (2009) S57–S273
treated orally from gestational day 7 to postnatal day 21 with PCB52, PCB138 or PCB180 at a dose of 1 mg/kg/day and the pups were kept for about 4 months. At the time of sacrifice, brain samples from cerebellum, striatum and whole blood were taken for gene expression analysis. The transcriptomics profiles revealed that (i) gender is a crucial biological variable influencing the genomic response, and (ii) response is PCB- and tissue-specific. The lists of differentially expressed gene probes were analyzed using pathway analysis tools. Functional analysis associated the gene lists with neurological disease and reaction of the immune system. Biological interaction networks related to neurological diseases could be generated from the male cerebellum samples and this indicated that male cerebellum is the most sensitive target in our setup. Gene expression analysis on whole blood of rats was used to (i) determine to what extent peripheral blood cells might react to systemic brain damage and (ii) to identify differentially expressed genes that may hold potential as an early molecular marker for neurological damage. Candidate blood biomarkers for PCB neurotox have been identified using convergent functional genomics.
were processed routinely, paraffin blocks were made and 6–7 micron were prepared and stained with Hematoxylin & Eosin. Results: Atypical hyperplasia was seen in the endometrial epithelium of the PCO group and in some of them carcinoma in the endometrium was observed. The morphometrical study showed an increase in height of epithelial endometrium and endometrial glands. Conclusion: In conclusion our results showed that sixty-three days estradiol valerate-induced PCO in rat could induce endometrial hyperplasia and even endometrial cancer, the conditions that may be observed in PCOS patients.
夽 Selected for Oral Presentation.
Y01 Nucleoplasmic bridge and nuclear bud are new biomarkers for biomonitoring of genetic damages induced by polycyclic aromatic hydrocarbons
doi:10.1016/j.toxlet.2009.06.827
J23 Estradiol valerate-induced atypical endometrial hyperplasia in experimental polycystic ovary Habib Allah Shojaei Saadi, Mohammad Amin Rezvanfar, Mohammad Abdollahi ∗ Tehran University of Medical Sciences, Faculty of Pharmacy, and Pharmaceutical Sciences Research Centre, Toxicology, Tehran, Iran, Islamic Republic of Iran Introduction: Polycystic ovarian syndrome (PCOS) is the most common and least understood endocrine disorder affecting approximately 5% of women of reproductive age. Women with PCOS are also at significantly higher risk of endometrial hyperplasia and endometrial cancer. It is shown that the animal models of the human PCO syndrome particularly rat have provided useful information on the morphologic and hormonal disturbances involved in the pathogenesis of chronic anovulation. The aim of this study was to evaluate the endometrium pathological changes of the estradiol valerate-induced PCO in rat. Methods: In this experiment, 32 rats (average weight 146 ± 1.6 g) in treatment group, each administered with 0.4 mg/rat intramuscular estradiol valerate and 16 rats of control group received vehicle (sterile sesame oil) at the dose rate of 0.4 mg/rat once through intramuscular injection. Sixty-three days post-injection, the experimental rats were euthanized by using CO2 gas. Ovaries and uteri were removed to evaluate the histopathological and histomorphometrical changes of these EV-induced PCO animals. The tissues were processed routinely, paraffin blocks were made and 6–7 micron were prepared and stained with Hematoxylin & Eosin. Results: In this experiment, 32 rats (average weight 146 ± 1.6 g) in treatment group, each administered with 0.4 mg/rat intramuscular estradiol valerate and 16 rats of control group received vehicle (sterile sesame oil) at the dose rate of 0.4 mg/rat once through intramuscular injection. Sixty-three days post-injection, the experimental rats were euthanized by using CO2 gas. Ovaries and uteri were removed to evaluate the histopathological and histomorphometrical changes of these EV-induced PCO animals. The tissues
Keywords: Rat; Polycystic ovary; Estradiol valerate; Endometrial hyperplasia; Endometrial cancer doi:10.1016/j.toxlet.2009.06.828 Biomarker and Biomonitoring
Huawei Duan ∗ , Ping Bin, Chuanfeng Huang, Yadong Wang, Yufei Dai, Yuxin Zheng National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China Question: Coke oven workers are regularly exposed to polycyclic aromatic hydrocarbons (PAHs) and have a higher risk of developing lung cancer. Limited evidence has demonstrated the direct link between exposure to PAHs and early genetic damages in exposed workers. Can nucleoplasmic bridge (NPB) and nuclear bud (NBUD) be as biomarkers for assessing genetic damages by PAHs? Methods: In this cross-sectional study, we used NPBs and NBUDs as the markers of the chromosomal damages in peripheral blood lymphocytes among 141 PAH-exposed workers and 66 unexposed controls by the cytokinesis-block micronucleus (CBMN) test. Urinary 1-hydroxypyrene (1-OHP) was used as the index of PAHs internal exposure. Results: We found the frequencies of NPBs and NBUDs were significantly higher in PAH-exposed workers than in the controls (9.56 ± 0.32, 7.25 ± 0.33 versus 1.86 ± 0.18, 2.20 ± 0.22, respectively; P < 0.001 for both comparisons) and in a dose-dependent manner. The dose-related increase was also observed by integrating variables of micronuclei (MN), NPBs and NBUDs, although this increase was not found for MN frequency alone. There were significantly positive correlations between urinary 1-OHP concentrations and the frequencies of NPBs and NBUDs. Combining with principal component analysis, it revealed that NPBs and NBUDs are more susceptible to PAHs exposure. Conclusions: Our results indicate that NPBs and NBUDs are sensitive and effective biomarkers for genetic damages induced by PAHs exposure and could be used for the biomonitoring of PAH-exposed workers. doi:10.1016/j.toxlet.2009.06.744
Abstracts / Toxicology Letters 189S (2009) S57–S273
treated orally from gestational day 7 to postnatal day 21 with PCB52, PCB138 or PCB180 at a dose of 1 mg/kg/day and the pups were kept for about 4 months. At the time of sacrifice, brain samples from cerebellum, striatum and whole blood were taken for gene expression analysis. The transcriptomics profiles revealed that (i) gender is a crucial biological variable influencing the genomic response, and (ii) response is PCB- and tissue-specific. The lists of differentially expressed gene probes were analyzed using pathway analysis tools. Functional analysis associated the gene lists with neurological disease and reaction of the immune system. Biological interaction networks related to neurological diseases could be generated from the male cerebellum samples and this indicated that male cerebellum is the most sensitive target in our setup. Gene expression analysis on whole blood of rats was used to (i) determine to what extent peripheral blood cells might react to systemic brain damage and (ii) to identify differentially expressed genes that may hold potential as an early molecular marker for neurological damage. Candidate blood biomarkers for PCB neurotox have been identified using convergent functional genomics.
were processed routinely, paraffin blocks were made and 6–7 micron were prepared and stained with Hematoxylin & Eosin. Results: Atypical hyperplasia was seen in the endometrial epithelium of the PCO group and in some of them carcinoma in the endometrium was observed. The morphometrical study showed an increase in height of epithelial endometrium and endometrial glands. Conclusion: In conclusion our results showed that sixty-three days estradiol valerate-induced PCO in rat could induce endometrial hyperplasia and even endometrial cancer, the conditions that may be observed in PCOS patients.
夽 Selected for Oral Presentation.
Y01 Nucleoplasmic bridge and nuclear bud are new biomarkers for biomonitoring of genetic damages induced by polycyclic aromatic hydrocarbons
doi:10.1016/j.toxlet.2009.06.827
J23 Estradiol valerate-induced atypical endometrial hyperplasia in experimental polycystic ovary Habib Allah Shojaei Saadi, Mohammad Amin Rezvanfar, Mohammad Abdollahi ∗ Tehran University of Medical Sciences, Faculty of Pharmacy, and Pharmaceutical Sciences Research Centre, Toxicology, Tehran, Iran, Islamic Republic of Iran Introduction: Polycystic ovarian syndrome (PCOS) is the most common and least understood endocrine disorder affecting approximately 5% of women of reproductive age. Women with PCOS are also at significantly higher risk of endometrial hyperplasia and endometrial cancer. It is shown that the animal models of the human PCO syndrome particularly rat have provided useful information on the morphologic and hormonal disturbances involved in the pathogenesis of chronic anovulation. The aim of this study was to evaluate the endometrium pathological changes of the estradiol valerate-induced PCO in rat. Methods: In this experiment, 32 rats (average weight 146 ± 1.6 g) in treatment group, each administered with 0.4 mg/rat intramuscular estradiol valerate and 16 rats of control group received vehicle (sterile sesame oil) at the dose rate of 0.4 mg/rat once through intramuscular injection. Sixty-three days post-injection, the experimental rats were euthanized by using CO2 gas. Ovaries and uteri were removed to evaluate the histopathological and histomorphometrical changes of these EV-induced PCO animals. The tissues were processed routinely, paraffin blocks were made and 6–7 micron were prepared and stained with Hematoxylin & Eosin. Results: In this experiment, 32 rats (average weight 146 ± 1.6 g) in treatment group, each administered with 0.4 mg/rat intramuscular estradiol valerate and 16 rats of control group received vehicle (sterile sesame oil) at the dose rate of 0.4 mg/rat once through intramuscular injection. Sixty-three days post-injection, the experimental rats were euthanized by using CO2 gas. Ovaries and uteri were removed to evaluate the histopathological and histomorphometrical changes of these EV-induced PCO animals. The tissues
Keywords: Rat; Polycystic ovary; Estradiol valerate; Endometrial hyperplasia; Endometrial cancer doi:10.1016/j.toxlet.2009.06.828 Biomarker and Biomonitoring
Huawei Duan ∗ , Ping Bin, Chuanfeng Huang, Yadong Wang, Yufei Dai, Yuxin Zheng National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China Question: Coke oven workers are regularly exposed to polycyclic aromatic hydrocarbons (PAHs) and have a higher risk of developing lung cancer. Limited evidence has demonstrated the direct link between exposure to PAHs and early genetic damages in exposed workers. Can nucleoplasmic bridge (NPB) and nuclear bud (NBUD) be as biomarkers for assessing genetic damages by PAHs? Methods: In this cross-sectional study, we used NPBs and NBUDs as the markers of the chromosomal damages in peripheral blood lymphocytes among 141 PAH-exposed workers and 66 unexposed controls by the cytokinesis-block micronucleus (CBMN) test. Urinary 1-hydroxypyrene (1-OHP) was used as the index of PAHs internal exposure. Results: We found the frequencies of NPBs and NBUDs were significantly higher in PAH-exposed workers than in the controls (9.56 ± 0.32, 7.25 ± 0.33 versus 1.86 ± 0.18, 2.20 ± 0.22, respectively; P < 0.001 for both comparisons) and in a dose-dependent manner. The dose-related increase was also observed by integrating variables of micronuclei (MN), NPBs and NBUDs, although this increase was not found for MN frequency alone. There were significantly positive correlations between urinary 1-OHP concentrations and the frequencies of NPBs and NBUDs. Combining with principal component analysis, it revealed that NPBs and NBUDs are more susceptible to PAHs exposure. Conclusions: Our results indicate that NPBs and NBUDs are sensitive and effective biomarkers for genetic damages induced by PAHs exposure and could be used for the biomonitoring of PAH-exposed workers. doi:10.1016/j.toxlet.2009.06.744