DNA damage in mouse organs and in human sperm cells by bisphenol A

Sharma, Anoop; Boberg, Julie; Dybdahl, Marianne

doi:10.1080/02772248.2018.1529236

Cited by 4 publications

(4 citation statements)

References 32 publications

(45 reference statements)

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“…[ 61 ] Male mice exposed to BPA at 125, 250, and 500 mg/kg bw by oral gavage showed a significant increase in testicular DNA strand breaks. [ 62 ] Significantly increased the % TUNEL positive (apoptotic) cauda epididymis sperms were observed in BPA + DIA exposed animals compared to control, BPA, and DIA groups. Previously, it has been reported that BPA exposure to male BALB/c mice (1 mg/kg bw) through per oral route for 4 consecutive weeks showed an increase in the number of TUNEL‐positive germ cells.…”

Section: Discussionmentioning

confidence: 99%

Studies on male gonadal toxicity of bisphenol A in diabetic rats: An example of exacerbation effect

Sahu

Singla

Jena

2022

J Biochem & Molecular Tox

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Bisphenol A (BPA), a widely used organic synthetic chemical alters spermatogenesis and is a potential risk factor for male infertility. Diabetes-induced hyperglycemia has a negative impact on different vital organs including the testis. However, the effect of BPA on male fertility and gonadal development in diabetic (DIA) patients is unknown. This study explores the role of BPA exposure on testicular toxicity in a DIA rat. The DIA condition in male Sprague-Dawley (SD) rats (4 weeks aged) was induced with the administration of a single dose of streptozotocin (55 mg/kg ip, in cold citrate buffer pH 4.5). BPA was administered orally at the dose of 40 mg/kg/day for 4 consecutive weeks. Various endpoints of the toxicity include biochemical estimations, histological evaluations, oxidative stress parameters, DNA damage assays (apoptosis and endonuclease III), expressions of 8-hydroxy-2ʹ-deoxyguanosine (8-OHdG), nuclear factor-erythroid 2-related factor 2 (Nrf-2), catalase, superoxide dismutase 1 (SOD-1), octamer-binding transcription factor 4 (OCT4), and Sirtulin (silent mating type information regulation 2 homolog) 1 (SIRT 1). The results confirmed that BPA exacerbated the testicular toxicity by altering several biochemical parameters, increasing oxidative stress, cellular/tissue injury, DNA damage, apoptosis, and 8-OHdG expression, while decreasing the levels of Nrf-2, catalase, SOD-1, OCT4, and SIRT1 expressions in the testes of DIA rat. Linear regression analyses indicated a positive correlation between apoptosis and 8-OHdG, OCT4, and DNA damage (nuclear diffusion factor and tail length). The present study confirmed that BPA exposure in DIA conditions exacerbated the testicular damages in SD rats.Therefore, the DIA condition might have increased male gonadal toxicity due to BPA exposure and requires further attention to maintain their normal reproductive health.

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Section: Discussionmentioning

confidence: 99%

Studies on male gonadal toxicity of bisphenol A in diabetic rats: An example of exacerbation effect

Sahu

Singla

Jena

2022

J Biochem & Molecular Tox

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“…Among the five oral studies selected, three were positive and two were negative. A single study of high relevance reported negative results in multiple mouse organs (liver, kidney, testes, urinary bladder, colon and lungs) after single treatment at three doses up to the MTD of 500 mg/kg bw (Sharma et al, 2018 [RefID 662‐G]). Negative results were also reported in rats exposed to 200 mg/kg bw per day orally for 10 days (de Flora et al, 2011 ).…”

Section: Assessmentmentioning

confidence: 99%

“…Induction of DNA strand breaks, detected by comet assay in vivo , was observed only after repeated exposure for extensive periods of time up to 8 weeks (Tiwari et al, 2012 ; Zhou et al, 2017c [RefID 9083]; Panpatil et al, 2020 [RefID 379‐G]). Only one study of high relevance was available on single administration of BPA reporting negative results in multiple mouse organs in a range of doses up to the MTD of 500 mg/kg bw (Sharma et al, 2018 [RefID 662‐G]). An indication of a possible role of the oxidative stress in inducing DNA strand breaks by BPA was provided by the results of several studies (Abdel‐Rahman et al, 2018 [RefID 199‐G]; Fawzy et al, 2018 [RefID 270‐G]; Kazmi et al, 2018 [RefID 315‐G]; Majid et al, 2019 [RefID 354‐G]; Mohammed et al, 2020 [RefID 363‐G]) showing the protective effects of natural extracts with antioxidant properties.…”

Section: Assessmentmentioning

confidence: 99%

Re‐evaluation of the risks to public health related to the presence of bisphenol A (BPA) in foodstuffs

Lambré¹,

Baviera²,

Bolognesi³

et al. 2023

EFS2

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In 2015, EFSA established a temporary tolerable daily intake (t‐TDI) for BPA of 4 μg/kg body weight (bw) per day. In 2016, the European Commission mandated EFSA to re‐evaluate the risks to public health from the presence of BPA in foodstuffs and to establish a tolerable daily intake (TDI). For this re‐evaluation, a pre‐established protocol was used that had undergone public consultation. The CEP Panel concluded that it is Unlikely to Very Unlikely that BPA presents a genotoxic hazard through a direct mechanism. Taking into consideration the evidence from animal data and support from human observational studies, the immune system was identified as most sensitive to BPA exposure. An effect on Th17 cells in mice was identified as the critical effect; these cells are pivotal in cellular immune mechanisms and involved in the development of inflammatory conditions, including autoimmunity and lung inflammation. A reference point (RP) of 8.2 ng/kg bw per day, expressed as human equivalent dose, was identified for the critical effect. Uncertainty analysis assessed a probability of 57–73% that the lowest estimated Benchmark Dose (BMD) for other health effects was below the RP based on Th17 cells. In view of this, the CEP Panel judged that an additional uncertainty factor (UF) of 2 was needed for establishing the TDI. Applying an overall UF of 50 to the RP, a TDI of 0.2 ng BPA/kg bw per day was established. Comparison of this TDI with the dietary exposure estimates from the 2015 EFSA opinion showed that both the mean and the 95th percentile dietary exposures in all age groups exceeded the TDI by two to three orders of magnitude. Even considering the uncertainty in the exposure assessment, the exceedance being so large, the CEP Panel concluded that there is a health concern from dietary BPA exposure.

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“…The OECD suggests that protocol modifications and validation studies are necessary before TG 489 can be revised to include an analysis of testicular germ cells. Nevertheless, the comet assay has been used to measure DNA damage in gonadal cells in both research settings (Asare et al, 2016; Bjorge et al, 1995; 1996a; Brunborg et al, 2015; Olsen et al, 2001; 2003; Collins, 2004; Olsen et al, 2005; Olive & Banath, 2006; Speit & Hartmann, 2006; Dhawan et al, 2009; Hansen et al, 2010; 2014; Graupner et al, 2014; 2015; Gutzkow et al, 2016 Graupner et al, 2017; Sharma et al, 2018) and in a regulatory perspective (Brendler‐Schwaab et al, 2005; Vasquez, 2012; Graupner et al, 2014; Frotschl, 2015; Koppen et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Assessing testicular germ cell DNA damage in the comet assay; introduction of a proof‐of‐concept

Dirven

Eide

Henriksson

et al. 2023

Environ and Mol Mutagen

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The in vivo comet assay is widely used to measure genotoxicity; however, the current OECD test guideline (TG 489) does not recommend using the assay to assess testicular germ cells, due to the presence of testicular somatic cells. An adapted approach to specifically assess testicular germ cells within the comet assay is certainly warranted, considering regulatory needs for germ cell-specific genotoxicity data in relation to the increasing global production of and exposure to potentially hazardous chemicals.

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DNA damage in mouse organs and in human sperm cells by bisphenol A

Cited by 4 publications

References 32 publications

Studies on male gonadal toxicity of bisphenol A in diabetic rats: An example of exacerbation effect

Studies on male gonadal toxicity of bisphenol A in diabetic rats: An example of exacerbation effect

Re‐evaluation of the risks to public health related to the presence of bisphenol A (BPA) in foodstuffs

Assessing testicular germ cell DNA damage in the comet assay; introduction of a proof‐of‐concept

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