Impact of endocrine disruptor hexachlorobenzene on the mammary gland and breast cancer: The story thus far

Miret, Noelia; Pontillo, Carolina; Zárate, Lorena Vanesa; Pisarev, Diana Kleiman de; Cocca, Claudia; Randi, Andrea

doi:10.1016/j.envres.2019.03.054

Cited by 40 publications

(32 citation statements)

References 125 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As previously described [ 12 ], MG development can be regarded as accelerated if the number of TEBs in the treated group is higher than that of the control at 3 weeks of age. Exposure to hexachlorobenzene (HCB) has been shown to increase the number of TEBs in C57BL/6 mice [ 56 ], which could increase the risk of breast cancer [ 57 – 59 ]. However, the opposite was observed in the present study and, thus, perinatal exposure to the High dose of POPs seemed to restrict MG development in 3-week-old female mice.…”

Section: Discussionmentioning

confidence: 99%

Perinatal exposure to a human relevant mixture of persistent organic pollutants: Effects on mammary gland development, ovarian folliculogenesis and liver in CD-1 mice

et al. 2021

View full text Add to dashboard Cite

The ability of persistent organic pollutants (POPs) with endocrine disrupting properties to interfere with the developing reproductive system is of increasing concern. POPs are transferred from dams to offspring and the high sensitivity of neonates to endocrine disturbances may be caused by underdeveloped systems of metabolism and excretion. The present study aimed to characterize the effect of in utero and lactational exposure to a human relevant mixture of POPs on the female mammary gland, ovarian folliculogenesis and liver function in CD-1 offspring mice. Dams were exposed to the mixture through the diet at Control, Low or High doses (representing 0x, 5000x and 100 000x human estimated daily intake levels, respectively) from weaning and throughout mating, gestation, and lactation. Perinatally exposed female offspring exhibited altered mammary gland development and a suppressed ovarian follicle maturation. Increased hepatic cytochrome P450 enzymatic activities indirectly indicated activation of nuclear receptors and potential generation of reactive products. Hepatocellular hypertrophy was observed from weaning until 30 weeks of age and could potentially lead to hepatotoxicity. Further studies should investigate the effects of human relevant mixtures of POPs on several hormones combined with female reproductive ability and liver function.

show abstract

Section: Discussionmentioning

confidence: 99%

Perinatal exposure to a human relevant mixture of persistent organic pollutants: Effects on mammary gland development, ovarian folliculogenesis and liver in CD-1 mice

et al. 2021

View full text Add to dashboard Cite

show abstract

“…In breast tissue, the binding of HCB to the AHR can activate both membrane (c‐Src) and nuclear pathways. By activating c‐Src, AHR can interact with other membrane receptors, including estrogen receptor‐α, insulin‐like growth factor‐1 receptor, epidermal growth factor receptor and transforming growth factor‐beta 1 receptor (Miret et al., 2019; Starek‐Swiechowicz et al., 2017). Our study showed that AHR was expressed in four different types of testicular cells, with the highest expression levels in TM3 cells, although the overall expression levels did not differ significantly.…”

Section: Discussionmentioning

confidence: 99%

“…Because only a limited amount of data was available for Mus musculus , we extended our search to include Homo sapiens . As a weak ligand of HCB, the aryl hydrocarbon receptor (AHR) also plays an important role in tissue injuries related to HCB (Chiappini et al., 2019; Miret et al., 2019). Proteins interacting with the AHR were identified by searching BioGRID (http://thebiogrid.org/), I2D (http://ophid.utoronto.ca/ophidv2.204/index.jsp) (Brown & Jurisica, 2007) and the Agile Protein Interactomes DataServer (http://cicblade.dep.usal.es:8080/APID/) (Alonso‐Lopez et al., 2019) databases.…”

Section: Methodsmentioning

confidence: 99%

Section: Screening and Identification Of Genes That Interacted With Hcbmentioning

confidence: 99%

See 1 more Smart Citation

The endocrine disruptor hexachlorobenzene can cause oxidative damage in the testis of mice

Dou

Mou

et al. 2021

Andrologia

View full text Add to dashboard Cite

Hexachlorobenzene (HCB) was originally used as a common pesticide but was subsequently identified as an endocrine-disrupting chemical (Chiappini et al., 2019). Consequently, the use of HCB as a pesticide was terminated in the mid-1970s and is only used in laboratory scenarios at present (Iatrou et al., 2019;Yu et al., 2019). However, since HCB degrades slowly in natural environments and can accumulate in organisms, HCB residues have been detected in soil, water, humans, animals and plants in many regions and countries across the world. As a consequence, HCB remains one of the largest environmental pol-

show abstract

“…136 These mammary gland effects of HCB have been proposed as being due to activation of the Ah receptor, which influences insulin growth factor, transforming growth factor beta 1, and estrogen receptor signaling pathways. 137 Maxillary incisor degeneration was observed in animals administered HCB at doses of ≥1 mg/kg/day. The morphology and distribution of HCB-induced incisor lesions in rats are consistent with injury to a selective population of preodontoblasts and support a direct cytotoxic mechanism of action.…”

Section: Core Studymentioning

confidence: 99%

NTP Technical Report on the Toxicity Studies of Hexachlorobenzene (CASRN 118-74-1) Administered by Gavage to Female Sprague Dawley (Hsd:Sprague Dawley® SD®) Rats

2021

View full text Add to dashboard Cite

Despite the cessation of its production and use in many parts of the world, hexachlorobenzene (HCB) remains highly persistent in the environment, and chronic, low-dose exposure to HCB in humans continues. Its structural resemblance to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), ability to activate the aryl hydrocarbon (Ah) receptor, TCDD-like toxicities, and bioaccumulative nature suggest HCB be included in the toxic equivalency factor (TEF) methodology. Consequently, the National Toxicology Program conducted this subchronic study of HCB, including measurement of a variety of toxicological and biochemical endpoints, to allow comparison to TCDD data obtained in a previous 2-year bioassay. Groups of 10 female Sprague Dawley (Hsd:Sprague Dawley ® SD ®) rats (core study) were administered doses of 0.03, 0.1, 0.3, 1, 3, 10, or 25 mg HCB/kg body weight/day (mg/kg/day) in corn oil:acetone (99:1) by gavage, 5 days/week for 13 weeks (3 months). Elimination of HCB after repeated dosing was evaluated in a group of 10 female rats (elimination study) administered 0.03 or 25 mg/kg/day for 13 weeks (3 months) and then held without dosing until necropsy at 21 (5 rats) or 29 (5 rats) weeks. Vehicle control female rats (10 core study and 10 elimination study) were administered the corn oil:acetone vehicle only. Genotoxicity in Salmonella typhimurium was also evaluated.

show abstract

Impact of endocrine disruptor hexachlorobenzene on the mammary gland and breast cancer: The story thus far

Cited by 40 publications

References 125 publications

Perinatal exposure to a human relevant mixture of persistent organic pollutants: Effects on mammary gland development, ovarian folliculogenesis and liver in CD-1 mice

Perinatal exposure to a human relevant mixture of persistent organic pollutants: Effects on mammary gland development, ovarian folliculogenesis and liver in CD-1 mice

The endocrine disruptor hexachlorobenzene can cause oxidative damage in the testis of mice

NTP Technical Report on the Toxicity Studies of Hexachlorobenzene (CASRN 118-74-1) Administered by Gavage to Female Sprague Dawley (Hsd:Sprague Dawley® SD®) Rats

Contact Info

Product

Resources

About