Effects of Benzophenone-3 and Propylparaben on Estrogen Receptor–Dependent R-Loops and DNA Damage in Breast Epithelial Cells and Mice

Majhi, Prabin D.; Sharma, Ajeet D.; Roberts, Angela; Daniele, Elizabeth; Majewski, A; Chuong, Lynn M.; Black, Amye L.; Vandenberg, Laura N.; Schneider, Sallie S.; Dunphy, Karen A.; Jerry, D. Joseph

doi:10.1289/ehp5221

Cited by 48 publications

(21 citation statements)

References 82 publications

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“…Propylparaben is a kind of xenoestrogen and exerts neuroprotective effects in neurodegenerative diseases such as Alzheimer’s disease ( 37 ). However, an acute exposure to propylparaben may cause DNA damage in mice ( 38 ). Since its mixed directionality of association with health, the role of Propylparaben in frailty is worthy of further study.…”

Section: Discussionmentioning

confidence: 99%

Distinct Serum and Fecal Metabolite Profiles Linking With Gut Microbiome in Older Adults With Frailty

et al. 2022

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Frailty is a critical aging-related syndrome but the underlying metabolic mechanism remains poorly understood. The aim of this study was to identify novel biomarkers and reveal potential mechanisms of frailty based on the integrated analysis of metabolome and gut microbiome. In this study, twenty subjects consisted of five middle-aged adults and fifteen older adults, of which fifteen older subjects were divided into three groups: non-frail, pre-frail, and frail, with five subjects in each group. The presence of frailty, pre-frailty, or non-frailty was established according to the physical frailty phenotype (PFP). We applied non-targeted metabolomics to serum and feces samples and used 16S rDNA gene sequencing to detect the fecal microbiome. The associations between metabolites and gut microbiota were analyzed by the Spearman’s correlation analysis. Serum metabolic shifts in frailty mainly included fatty acids and derivatives, carbohydrates, and monosaccharides. Most of the metabolites belonging to these classes increased in the serum of frail older adults. Propylparaben was found to gradually decrease in non-frail, pre-frail, and frail older adults. Distinct changes in fecal metabolite profiles and gut microbiota were also found among middle-aged adults, non-frail and frail older subjects. The relative abundance of Faecalibacteriu, Roseburia, and Fusicatenibacter decreased while the abundance of Parabacteroides and Bacteroides increased in frailty. The above altered microbes were associated with the changed serum metabolites in frailty, which included dodecanedioic acid, D-ribose, D-(-)-mannitol, creatine and indole, and their related fecal metabolites. The changed microbiome and related metabolites may be used as the biomarkers of frailty and is worthy of further mechanistic studies.

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Section: Discussionmentioning

confidence: 99%

Distinct Serum and Fecal Metabolite Profiles Linking With Gut Microbiome in Older Adults With Frailty

et al. 2022

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“…But the tissue specificity of disruptions in homology-directed repair remain a significant question as increased error-prone DNA repair in BALB/cMed- Trp53 +/− mice would increase the potential for pathogenic mutations in all tissues. The estrogen receptor α (ERα) has been shown to induce DSBs in breast cancer cell lines and in the mammary epithelium of BALB/c mice even in the absence of proliferation [ 45 ]. Therefore, the luminal cells of the mammary epithelium would be subjected to continuous DNA damage which, together with the replication stress and error-prone repair through SSA, would increase the probability of acquiring oncogenic mutations [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic modifiers regulating DNA replication and double-strand break repair are associated with differences in mammary tumors in mouse models of Li-Fraumeni syndrome

et al. 2021

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Breast cancer is the most common tumor among women with inherited variants in the TP53 tumor suppressor, but onset varies widely suggesting interactions with genetic or environmental factors. Rodent models haploinsufficent for Trp53 also develop a wide variety of malignancies associated with Li-Fraumeni Syndrome, but BALB/c mice are uniquely susceptible to mammary tumors and is genetically linked to the Suprmam1 locus on chromosome 7. To define mechanisms that interact with deficiencies in p53 to alter susceptibility to mammary tumors, we fine-mapped the Suprmam1 locus in females from an N2 backcross of BALB/cMed and C57BL/6J mice. A major modifier was localized within a 10 cM interval on chromosome 7. The effect of the locus on DNA damage responses was examined in the parental strains and mice that are congenic for C57BL/6J alleles on the BALB/cMed background (SM1- Trp53 +/− ). The mammary epithelium of C57BL/6J- Trp53 +/− females exhibited little radiation-induced apoptosis compared to BALB/cMed- Trp53 +/− and SM1- Trp53 +/− females indicating that the Suprmam1 B6/B6 alleles could not rescue repair of radiation-induced DNA double-strand breaks mostly relying on non-homologous end joining. In contrast, the Suprmam1 B6/B6 alleles in SM1- Trp53 +/− mice were sufficient to confer the C57BL/6J- Trp53 +/− phenotypes in homology-directed repair and replication fork progression. The Suprmam1 B6/B6 alleles in SM1- Trp53 +/− mice appear to act in trans to regulate a panel of DNA repair and replication genes which lie outside the locus. Significance: Genetic variation in replication-associated DNA repair can modify consequences of heterozygous mutations in Trp53 and contribute to susceptibility to mammary tumors in mouse models of Li-Fraumeni syndrome.

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“…Benzophenone-3 has also been shown to increase uterine weight in ovariectomized rat females (Schlumpf et al, 2001;Schlecht et al, 2004;Suzuki et al, 2005). The effect of benzophenone-3 on steroid hormones is not limited to direct effects on hormones but also involves damage to DNA fragments through a mechanism dependent on ERα estrogen receptors (Almeida et al, 2019;Majhi et al, 2020). The latest data from zebrafish show that benzophenone-3 affects estradiol biosynthesis, sex differentiation and gonadotropin-releasing hormone levels.…”

Section: Effects Of Benzophenone-3 On the Endocrine Systemsmentioning

confidence: 99%

Is the commonly used UV filter benzophenone-3 a risk factor for the nervous system?

Wnuk

Kajta

2021

Acta Biochim Pol

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Benzophenone-3 (2-hydroxy-4-methoxybenzophenone, oxybenzone, or BP-3) is one of the most frequently used UV radiation absorbents, which are commonly referred to as sunscreen filters. Its widespread use in industrial applications provides protection against the photodegradation of a wide range of products but at the same time creates the risk of human exposure to benzophenone-3 unbeknownst to the individuals exposed. Topically applied benzophenone-3 penetrates individual skin layers, enters the bloodstream, and is excreted in the urine. In addition, benzophenone-3 easily crosses the placental barrier, which creates the risk of exposure to this substance in the prenatal period. Despite the widespread use and occurrence of benzophenone-3 in the human environment, little knowledge of the mechanisms underlying the effect of benzophenone-3 on the nervous system was available until recently. Only the most recent research, including studies by our group, has enabled the identification of new molecular mechanisms through which benzophenone-3 affects embryonic neuronal cells and the developing mammalian brain. Benzophenone-3 has been shown to induce neurotoxicity and apoptotic processes and inhibit autophagy in embryonic neuronal cells. Benzophenone-3 also alters expression and impairs function of receptors necessary for the proper development and function of the nervous system. The most worrying finding seems to be that benzophenone-3 contributes to an increased risk of developmental abnormalities and/or epigenetically based degeneration of neuronal cells by changing the epigenetic status of neuronal cells.

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Effects of Benzophenone-3 and Propylparaben on Estrogen Receptor–Dependent R-Loops and DNA Damage in Breast Epithelial Cells and Mice

Cited by 48 publications

References 82 publications

Distinct Serum and Fecal Metabolite Profiles Linking With Gut Microbiome in Older Adults With Frailty

Distinct Serum and Fecal Metabolite Profiles Linking With Gut Microbiome in Older Adults With Frailty

Genetic modifiers regulating DNA replication and double-strand break repair are associated with differences in mammary tumors in mouse models of Li-Fraumeni syndrome

Is the commonly used UV filter benzophenone-3 a risk factor for the nervous system?

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