Mutagenicity and DNA Damage of Bisphenol a and its Structural Analogues in Hepg2 Cells

Fic, Anja; Žegura, Bojana; Dolenc, Marija Sollner; Filipič, Metka; Mašič, Lucíja Peterlin

doi:10.2478/10004-1254-64-2013-2319

Cited by 105 publications

(84 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These observations are in agreement with a limited amount of human evidence including a small retrospective study which found BPA levels in the urine of PCa patients were higher than in non-PCa patients (Tarapore et al 2014). Multiple mechanisms have been proposed for BPA action, including epigenetic reprogramming of gene expression (Ho et al 2006, Tang et al 2012), increased expansion of stem like progenitor cells in the prostate (Prins et al 2014), altering biosynthesis pathways such as the SNORDs (Ho et al 2015), disrupting the MTs (Pfeiffer et al 1997, Ochi 1999), causing adduct formation and DNA damage (Fic et al 2013) and increasing CA (Tarapore et al 2014). Centrosomes are the MT-organizing center in cells and via this process regulate cell orientation, polarity and migration.…”

Section: Discussionmentioning

confidence: 99%

Bisphenol A and its analogues disrupt centrosome cycle and microtubule dynamics in prostate cancer

Ho¹,

Rao²,

To³

et al. 2017

Endocrine-Related Cancer

View full text Add to dashboard Cite

Humans are increasingly exposed to structural analogues of bisphenol A (BPA), as BPA is being replaced by these compounds in BPA-free consumer products. We have previously shown that chronic and developmental exposure to BPA is associated with increased prostate cancer (PCa) risk in human and animal models. Here we examine whether exposure of PCa cells (LNCaP, C4-2) to low-dose BPA and its structural analogues (BPS, BPF, BPAF, TBBPA, DMBPA and TMBPA) affects centrosome amplification (CA), a hallmark of cancer initiation and progression. We found that exposure to BPA, BPS, DMBPA and TBBPA in descending order, increased number of cells with CA, in a non-monotonic dose-response manner. Furthermore, cells treated with BPA and these analogues initiated centrosome duplication at 8h post-release from serum-starvation, significantly earlier in G-1 phase than control cells. This response was attended by earlier release of nucleophosmin from unduplicated centrosomes. BPA exposed cells exhibited increased expression of cyclin dependent kinase CDK6, and decreased expression of CDK inhibitors (p21Waf1/CIP1, p27KIP1). Using specific antagonists for estrogen/androgen receptors, CA in presence of BPA or its analogues was likely to be mediated via ESR1 signaling. Change in microtubule dynamics was observed on exposure to these analogues, which, for BPA, was accompanied by increased expression of centrosome-associated protein CEP350. Similar to BPA, chronic treatment of cells with DMBPA, but not other analogues, resulted in enhancement of anchorage-independent growth. We thus conclude that selected BPA analogues, similar to BPA, disrupt centrosome function and microtubule organization, with DMBPA displaying the broadest spectrum of cancer-promoting effects.

show abstract

Section: Discussionmentioning

confidence: 99%

Bisphenol A and its analogues disrupt centrosome cycle and microtubule dynamics in prostate cancer

Ho¹,

Rao²,

To³

et al. 2017

Endocrine-Related Cancer

View full text Add to dashboard Cite

show abstract

“…These observations were later extended upon by increased time to hatch, reduced number of sperm, increasing number of female to male ratio, and changes in the levels of testosterone, estradiol, and vitellogenin (Naderi et al 2014). In further experiments provided in cell cultures it has been demonstrated that BPS acts cytotoxically, genotoxically , and mutagenically (Fic et al 2013).…”

Section: Biological Effects Of Bpsmentioning

confidence: 95%

Bisphenol S instead of bisphenol A: a story of reproductive disruption by regretable substitution - a review

Žalmanová¹,

Hošková²,

Nevoral³

et al. 2016

Czech J. Anim. Sci.

View full text Add to dashboard Cite

A range of substances that are released into the environment, foodstuffs and drinking water as a result of human activity were originally considered relatively harmless, and it was only later that their adverse effects were discovered. In general the use of such substances is currently restricted, and they are often replaced by other substances. This applies also in the case of a range of endocrine disruptors. These substances have the capacity to disturb the balance of physiological functions of the organism on the level of hormonal regulation, and their pleiotropic spectrum of effects is very difficult to predict. Endocrine disruptors include the currently intensively studied bisphenol A (BPA), a prevalent environmental pollutant and contaminant of both water and foodstuffs. BPA has a significantly negative impact on human health, particularly on the regulation mechanisms of reproduction, and influences fertility. The ever increasingly stringent restriction of the industrial production of BPA is leading to its replacement with analogues, primarily with bisphenol S (BPS), which is not subject to these restrictions and whose impacts on the regulation of reproduction have not yet been exhaustively studied. However, the limited number of studies at disposal indicates that BPS may be at least as harmful as BPA. There is therefore a potential danger that the replacement of BPA with BPS will become one of the cases of regrettable substitution, in which the newly used substances manifest similar or even worse negative effects than the substances which they have replaced. The objective of this review is to draw attention to ill-advised replacements of endocrine disruptors with substances whose effects are not yet tested, and which may represent the same risks for the environment, for the reproduction of males and females, and for human health as have been demonstrated in the case of the originally used substances.

show abstract

“…In this study, we developed a multi-parametric HCA assay along with the detection of c-H2AX and found that BPA and its analogues significantly altered the expression levels of c-H2AX. It has been reported that BPA and its analogues induced DNA damages in a cell-type-specific and dose-dependent manner (Fic et al, 2013;Lee et al, 2013). BPA is able to induce DNA damage in spermatozoa , and in human breast cell line MCF-7 cells at the low concentration of 10 nM Pfeifer et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

High-Content Analysis Provides Mechanistic Insights into the Testicular Toxicity of Bisphenol A and Selected Analogues in Mouse Spermatogonial Cells

Liang

Yin

et al. 2016

Toxicol. Sci.

View full text Add to dashboard Cite

Bisphenol A (BPA), an endocrine-disrupting compound, was found to be a testicular toxicant in animal models. Bisphenol S (BPS), bisphenol AF (BPAF), and tetrabromobisphenol A (TBBPA) were recently introduced to the market as alternatives to BPA. However, toxicological data of these compounds in the male reproductive system are still limited so far. This study developed and validated an automated multi-parametric high-content analysis (HCA) using the C18-4 spermatogonial cell line as a model. We applied these validated HCA, including nuclear morphology, DNA content, cell cycle progression, DNA synthesis, cytoskeleton integrity, and DNA damage responses, to characterize and compare the testicular toxicities of BPA and 3 selected commercial available BPA analogues, BPS, BPAF, and TBBPA. HCA revealed BPAF and TBBPA exhibited higher spermatogonial toxicities as compared with BPA and BPS, including dose-and time-dependent alterations in nuclear morphology, cell cycle, DNA damage responses, and perturbation of the cytoskeleton. Our results demonstrated that this specific culture model together with HCA can be utilized for quantitative screening and discriminating of chemical-specific testicular toxicity in spermatogonial cells. It also provides a fast and cost-effective approach for the identification of environmental chemicals that could have detrimental effects on reproduction.

show abstract

Mutagenicity and DNA Damage of Bisphenol a and its Structural Analogues in Hepg2 Cells

Cited by 105 publications

References 52 publications

Bisphenol A and its analogues disrupt centrosome cycle and microtubule dynamics in prostate cancer

Bisphenol A and its analogues disrupt centrosome cycle and microtubule dynamics in prostate cancer

Bisphenol S instead of bisphenol A: a story of reproductive disruption by regretable substitution - a review

High-Content Analysis Provides Mechanistic Insights into the Testicular Toxicity of Bisphenol A and Selected Analogues in Mouse Spermatogonial Cells

Contact Info

Product

Resources

About