Modulation of ovarian follicle maturation and effects on apoptotic cell death in holtzman rats exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD) in utero and lactationally

Heimler, Ira; Trewin, Amanda L.; Chaffin, Charles L.; Rawlins, Richard G.; Hutz, Reinhold J.

doi:10.1016/s0890-6238(97)00101-9

Cited by 88 publications

(51 citation statements)

References 23 publications

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“…Importantly, some of the phenotypes observed in the Ah -/-mice are similar to those reported in TCDD-treated animals, suggesting that the endogenous AHR responds to endogenous signals. Notably, Ah -/-mice exhibit defects in reproduction and ovary development, and these defects are also observed in wild type mice treated with TCDD [17][18][19][20]. Collectively, these findings support the hypothesis that a reduction in the level of endogenous AHR protein may reduce responsiveness to endogenous signaling molecules and possibly contribute to the biological effects mediated by TCDD.…”

Section: Introductionsupporting

confidence: 67%

Specific blockage of ligand-induced degradation of the Ah receptor by proteasome but not calpain inhibitors in cell culture lines from different species

Pollenz

2007

Biochemical Pharmacology

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To firmly establish the pathway involved in ligand-induced degradation of the AHR, cell lines derived from mouse rat or human tissues were exposed to inhibitors specific to the proteasome or calpain proteases and exposed to TCDD. The level of endogenous AHR and CYP1A1 protein was then evaluated by quantitative Western blotting. Treatment of cells with the calpain inhibitors: calpeptin, calpain inhibitor III, or PD150606 either individually or in combinations up to 75μM did not reduce TCDD-induced degradation of the AHR, the induction of endogenous CYP1A1 or the nuclear accumulation of the AHR. The activity of the inhibitors was verified with an in vivo calpain assay. In contrast, exposure of cells to the specific proteasome inhibitors: epoxomicin (1-5μM), proteasome inhibitor I (5-10μM) or lactacystin (5-15μM) completely inhibited TCDD-induced degradation of the AHR. Inhibition of AHR degradation with these compounds did not reduce the induction of endogenous CYP1A1. In addition, exposure of the Hepa-1 line to the various proteasome inhibitors caused an accumulation of the AHR in the nucleus in the absence of TCDD exposure. Finally, Western blot analysis of the DNA bound AHR showed that its molecular mass was unchanged in comparison to the unliganded (cytoplasmic) AHR. Thus, these studies conclusively implicate the proteasome and not calpain proteases in the ligand-induced degradation of the mouse, rat and human AHR and suggest that the pharmacological use of proteasome inhibitors may impact the time course and magnitude of gene regulatory events mediated through the AHR.

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Section: Introductionsupporting

confidence: 67%

Specific blockage of ligand-induced degradation of the Ah receptor by proteasome but not calpain inhibitors in cell culture lines from different species

Pollenz

2007

Biochemical Pharmacology

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“…TCDD is a teratogen and developmental toxicant in many species but is especially potent at inducing hydronephrosis and cleft palate in mouse embryos (Birnbaum, 1994). TCDD can also affect the endocrine and reproductive systems (Peterson et al, 1993;Birnbaum, 1994;Heimler et al, 1998), as well as the development of other organ systems (Sakamoto et al, 1995;Henshel, 1998;MacLusky et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

2,3,7,8-Tetrachlorodibenzo-p-dioxin induces apoptotic cell death and cytochrome P4501A expression in developing Fundulus heteroclitus embryos

et al. 2001

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“…Because substantial animal and limited human evidence has suggested that in utero and early childhood exposure may affect reproductive health (Birnbaum 1995;Brown et al 1998;Chaffin et al 1996;Eskenazi et al 2002b;Gray and Ostby 1995;Heimler et al 1998;Mocarelli et al 2000;Murray et al 1979;Nau et al 1986;Petroff et al 2000;Roman and Peterson 1998), 20 years after the explosion we initiated the Seveso Women's Health Study (SWHS), a historical cohort study to evaluate the association of TCDD exposure and reproductive outcomes among female residents. As part of this investigation, stored serum samples were analyzed for TCDD from a sample of the female population residing in zones A and B.…”

mentioning

confidence: 99%

Relationship of serum TCDD concentrations and age at exposure of female residents of Seveso, Italy.

Eskenazi

Mocarelli

Warner

et al. 2004

Environ Health Perspect

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In 1976, a chemical plant explosion near Seveso, Italy, resulted in the highest known exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in residential populations. In 1996, we initiated the Seveso Women's Health Study (SWHS), a historical cohort study of females who were ≤ 40 years old at the time of explosion and residents of the most heavily contaminated areas, zones A and B. Serum samples collected near the time of the explosion were analyzed for TCDD. We also analyzed pooled serum samples collected in 1976 from females who resided in zone non-ABR, the "unexposed" zone, to assess concurrent background exposures to other dioxins, furans, and coplanar polychlorinated biphenyls (PCBs). The median lipid-adjusted TCDD level for residents of zones A and B combined was 56 ppt (range = 2.5-56,000 ppt). Zone A residents had 5-fold higher TCDD levels (n = 67, median = 272 ppt) than did zone B residents (n = 814, median = 47 ppt). The youngest children had the highest TCDD levels, which decreased with age at explosion until approximately 13 years of age and were constant thereafter. Therefore, children living in zones A and B received a disproportionately higher exposure to TCDD as a result of the explosion. Zone of residence and age were the strongest predictors of TCDD level. Chloracne, nearby animal mortality, location (outdoors vs. indoors) at the time of explosion, and consumption of homegrown food were also related to serum TCDD levels. The serum pools from zone non-ABR residents had an average TCDD concentration of 20.2 ppt, and average total toxic equivalent (TEQ) concentration of 100.4 ppt. Therefore, background exposure to dioxins, furans, and PCBs unrelated to the explosion may have been substantial. As a consequence, previous SWHS studies that considered only TCDD exposure may have underestimated health effects due to total TEQ concentrations.

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Modulation of ovarian follicle maturation and effects on apoptotic cell death in holtzman rats exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD) in utero and lactationally

Cited by 88 publications

References 23 publications

Specific blockage of ligand-induced degradation of the Ah receptor by proteasome but not calpain inhibitors in cell culture lines from different species

Specific blockage of ligand-induced degradation of the Ah receptor by proteasome but not calpain inhibitors in cell culture lines from different species

2,3,7,8-Tetrachlorodibenzo-p-dioxin induces apoptotic cell death and cytochrome P4501A expression in developing Fundulus heteroclitus embryos

Relationship of serum TCDD concentrations and age at exposure of female residents of Seveso, Italy.

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