Bisphenol A and Its Biomaterial Monomer Derivatives Alteration of in Vitro Cytochrome P450 Metabolism in Rat, Minipig, and Human

Cannon, Jonathan; Kostoryz, Elisabet L.; Russo, Kim A.; Smith, Robin; Yourtee, David M.

doi:10.1021/bm005564+

Cited by 20 publications

(14 citation statements)

References 22 publications

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“…It was shown that BisGMA at concentrations >0.1 mM caused an extreme depletion of the intracellular GSH pool as well as apoptosis in HGF (Engelmann et al 2004). Moreover, it was found that BisGMA significantly influences the activity of cytochrome P450 (Cannon et al 2000). An elevated activity of this mitochondrial enzyme complex may by associated with an increase of the intracellular concentration of ROS, which subsequently deplete the cells’ pool of detoxifying glutathione (Engelmann et al 2004; Sapone et al 2003).…”

Section: Discussionmentioning

confidence: 99%

Bisphenol A-glycidyl methacrylate induces a broad spectrum of DNA damage in human lymphocytes

et al. 2010

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Bisphenol A-glycidyl methacrylate (BisGMA) is monomer of dental filling composites, which can be released from these materials and cause adverse biologic effects in human cells. In the present work, we investigated genotoxic effect of BisGMA on human lymphocytes and human acute lymphoblastic leukemia cell line (CCRF-CEM) cells. Our results indicate that BisGMA is genotoxic for human lymphocytes. The compound induced DNA damage evaluated by the alkaline, neutral, and pH 12.1 version of the comet assay. This damage included oxidative modifications of the DNA bases, as checked by DNA repair enzymes EndoIII and Fpg, alkali-labile sites and DNA double-strand breaks. BisGMA induced DNA-strand breaks in the isolated plasmid. Lymphocytes incubated with BisGMA at 1 mM were able to remove about 50% of DNA damage during 120-min repair incubation. The monomer at 1 mM evoked a delay of the cell cycle in the S phase in CCRF-CEM cells. The experiment with spin trap—DMPO demonstrated that BisGMA induced reactive oxygen species, which were able to damage DNA. BisGMA is able to induce a broad spectrum of DNA damage including severe DNA double-strand breaks, which can be responsible for a delay of the cell cycle in the S phase.

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Section: Discussionmentioning

confidence: 99%

Bisphenol A-glycidyl methacrylate induces a broad spectrum of DNA damage in human lymphocytes

et al. 2010

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“…BPA has also been reported to interact with drug-and steroid-metabolizing activity of rat (111), pig (112), and human hepatic cytochrome P450s (113,114) by inhibition of activities, although these were measured at high micromolar concentrations of BPA. For example, testosterone 16␤-hydroxylase and testosterone 2␣-hydroxylase activities were inhibited by BPA at 100 m (69 and 74%, respectively) (111).…”

Section: Metabolism Of Bpamentioning

confidence: 99%

Large Effects from Small Exposures. III. Endocrine Mechanisms Mediating Effects of Bisphenol A at Levels of Human Exposure

2006

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Over 6 billion pounds per year of the estrogenic monomer bisphenol A (BPA) are used to manufacture polycarbonate plastic products, in resins lining metal cans, in dental sealants, and in blends with other types of plastic products. The ester bond linking BPA molecules in polycarbonate and resins undergoes hydrolysis, resulting in the release of free BPA into food, beverages, and the environment, and numerous monitoring studies now show almost ubiquitous human exposure to biologically active levels of this chemical. BPA exerts estrogenic effects through the classical nuclear estrogen receptors, and BPA acts as a selective estrogen receptor modulator. However, BPA also initiates rapid responses via estrogen receptors presumably associated with the plasma membrane. Similar to estradiol, BPA causes changes in some cell functions at concentrations between 1 pM and 1 nM, and the mean and median range of unconjugated BPA measured by multiple techniques in human pregnant maternal, fetal, and adult blood and other tissues exceeds these levels. In contrast to these published findings, BPA manufacturers persist in describing BPA as a weak estrogen and insist there is little concern with human exposure levels. Our concern with human exposure to BPA derives from 1) identification of molecular mechanisms mediating effects in human and animal tissues at very low doses, 2) in vivo effects in experimental animals caused by low doses within the range of human exposure, and 3) widespread human exposure to levels of BPA that cause adverse effects in animals.

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“…In addition, BPA may elicit biological responses by activation of kinase cascades (e.g., MAPK [12]) and by exhibiting antiandrogenic [13,14] and/or antithyroid activity [15]. Other reports have suggested that BPA increased bioavailability of sex steroid hormones by disrupting metabolic degradation [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

The Industrial Chemical Bisphenol A (BPA) Interferes with Proliferative Activity and Development of Steroidogenic Capacity in Rat Leydig Cells1

Nanjappa

Simon

Akingbemi

2012

Biology of Reproduction

122

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The presence of bisphenol A (BPA) in consumer products has raised concerns about potential adverse effects on reproductive health. Testicular Leydig cells are the predominant source of the male sex steroid hormone testosterone, which supports the male phenotype. The present report describes the effects of developmental exposure of male rats to BPA by gavage of pregnant and lactating Long-Evans dams at 2.5 and 25 μg/kg body weight from Gestational Day 12 to Day 21 postpartum. This exposure paradigm stimulated Leydig cell division in the prepubertal period and increased Leydig cell numbers in the testes of adult male rats at 90 days. Observations from in vitro experiments confirmed that BPA acts directly as a mitogen in Leydig cells. However, BPA-induced proliferative activity in vivo is possibly mediated by several factors, such as 1) protein kinases (e.g., mitogen-activated protein kinases or MAPK), 2) growth factor receptors (e.g., insulin-like growth factor 1 receptor-beta and epidermal growth factor receptors), and 3) the Sertoli cell-secreted anti-Mullerian hormone (also called Mullerian inhibiting substance). On the other hand, BPA suppressed protein expression of the luteinizing hormone receptor (LHCGR) and the 17beta-hydroxysteroid dehydrogenase enzyme (HSD17B3), thereby decreasing androgen secretion by Leydig cells. We interpret these findings to mean that the likely impact of deficits in androgen secretion on serum androgen levels following developmental exposure to BPA is alleviated by increased Leydig cell numbers. Nevertheless, the present results reinforce the view that BPA causes biological effects at environmentally relevant exposure levels and its presence in consumer products potentially has implication for public health.

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Bisphenol A and Its Biomaterial Monomer Derivatives Alteration of in Vitro Cytochrome P450 Metabolism in Rat, Minipig, and Human

Cited by 20 publications

References 22 publications

Bisphenol A-glycidyl methacrylate induces a broad spectrum of DNA damage in human lymphocytes

Bisphenol A-glycidyl methacrylate induces a broad spectrum of DNA damage in human lymphocytes

Large Effects from Small Exposures. III. Endocrine Mechanisms Mediating Effects of Bisphenol A at Levels of Human Exposure

The Industrial Chemical Bisphenol A (BPA) Interferes with Proliferative Activity and Development of Steroidogenic Capacity in Rat Leydig Cells1

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