Effects of polybrominated biphenyls on metabolism of testosterone by rat hepatic microsomes

Newton, John F.; Braselton, W. Emmett; Lepper, L.F.; McCormack, K. M.; Hook, Jerry B.

doi:10.1016/0041-008x(82)90033-3

Cited by 15 publications

(10 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, PBB-associated CpGs were more likely to be near nuclear hormone receptor transcription factor binding sites. This is consistent with the altered hormone metabolism seen in rat models exposed to PBBs [63][64][65]. PBB-associated CpGs also massively overlap with estradiol-associated CpGs, and the effect sizes of CpGs associated with estradiol is correlated with the effect sizes seen with PBB.…”

Section: Discussionsupporting

confidence: 81%

Exposure to polybrominated biphenyl (PBB) associates with genome-wide DNA methylation differences in peripheral blood

et al. 2019

View full text Add to dashboard Cite

In 1973, Michigan residents were exposed to polybrominated biphenyl (PBB) when it was accidentally added to farm animal feed. Highly exposed individuals and their children have experienced endocrine-related health problems, though the underlying mechanism behind these remains unknown. We investigated whether PBB exposure is associated with variation in DNA methylation in peripheral blood samples from 658 participants of the Michigan PBB registry using the MethylationEPIC BeadChip, as well as investigated what the potential function of the affected regions are and whether these epigenetic marks are known to associate with endocrine system pathways. After multiple test correction (FDR <0.05), 1890 CpG sites associated with total PBB levels. These CpGs were not enriched in any particular biological pathway, but were enriched in enhancer and insulator regions, and depleted in regions near the transcription start site or in CpG islands (p < 0.05). They were also more likely to be in ARNT and ESR2 transcription factor binding sites (p = 3.27e-23 and p = 1.62e-6, respectively), and there was significant overlap between CpGs associated with PBB and CpGs associated with estrogen (p < 2.2e-16). PBBassociated CpGs were also enriched for CpGs known to be associated with gene expression in blood (eQTMs) (p < 0.05). These eQTMs were enriched for pathways related to immune function and endocrine-related autoimmune disease (FDR <0.05). These results indicate that exposure to PBB is associated with differences in epigenetic marks that suggest that it is acting similarly to estrogen and is associated with dysregulated immune system pathways. ARTICLE HISTORY

show abstract

Section: Discussionsupporting

confidence: 81%

Exposure to polybrominated biphenyl (PBB) associates with genome-wide DNA methylation differences in peripheral blood

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Animal data suggests antiandrogenic effects of perinatal PBB exposure through increased metabolism of testosterone and decreased responsiveness to testosterone (McCormack et al 1979; Newton et al 1982). The polychlorinated biphenyl (PCB) congener PCB-138 has demonstrated evidence of anti-androgenic activity (Bonefeld-Jorgensen et al 2001), raising suspicion for antiandrogenic activity of PBB-138 (which accounts for 5–12% of the FireMaster mixture (Hass et al 1978).…”

Section: Discussionmentioning

confidence: 99%

“…The FireMaster mixture of PBBs may include congeners with estrogenic, anti-estrogenic, or antiandrogenic activity (McCormack et al 1979; Nakari and Pessala 2005; Newton et al 1982). Because of the possibility of varied effects, we began our study with a general exploratory hypothesis, that PBB exposure may affect a variety of GU conditions.…”

mentioning

confidence: 99%

Maternal Exposure to a Brominated Flame Retardant and Genitourinary Conditions in Male Offspring

Small¹,

DeCaro²,

Terrell³

et al. 2009

Environ Health Perspect

View full text Add to dashboard Cite

BackgroundThe upward trend in industrial nations in the incidence of male genitourinary (GU) conditions may be attributed to increased exposure to endocrine disruptors. Polybrominated biphenyl (PBB), a brominated flame retardant, is one such suspected endocrine disruptor.ObjectiveWe investigated the relationship between maternal serum levels of PBBs and GU conditions among male offspring exposed in utero.MethodsIn this cohort study of sons born to women accidentally exposed to PBBs during 1973–1974, we examined self-reported data on GU conditions among male offspring in relation to maternal serum PBB levels. We used generalized estimating equations to calculate odds ratios (ORs), controlling for gestational age at birth.ResultsOf 464 sons, 33 reported any GU condition (13 hernias, 10 hydroceles, 9 cryptorchidism, 5 hypospadias, and 1 varicocele). Four reported both hernia and hydrocele, and one both hernia and cryptorchidism. After adjustment for gestational age at birth, sons of highly exposed women (> 5 ppb) were twice as likely to report any GU condition compared with sons of the least exposed women [≤1 ppb; OR = 2.0; 95% confidence interval (CI), 0.8–5.1]. This risk was increased when we excluded sons born after the exposure but before the mother’s serum PBB measurement (OR = 3.1; 95% CI, 1.0–9.1). We found evidence of a 3-fold increase in reported hernia or hydrocele among sons with higher PBB exposure (test of trend p-value = 0.04). Neither hypospadias nor cryptorchidism was individually associated with PBB exposure.ConclusionsAlthough cryptorchidism and hypospadias were not associated with in utero PBB exposure, this study suggests that other GU conditions may be associated with exposure to endocrine-disrupting chemicals during development.

show abstract

“…A dietary concentration of 100 mg PBBs kg -I caused decreased egg production and nesting behavior in Japanese quail . Newton et al (1982) r,eported increased hydroxylation rates of testosterone to 7a-and 6/3-hydroxytestosterone in rats fed 100 mg kg -I PBB for 4 mono A reduction of testosterone to dihydrotestosterone and dihydroandrosterone also was found in microsomes from both sexes. Byrne et al (1988) fed rats for 5-7 mon with doses of 1-50 mg kg-I food.…”

Section: G Effects On Reproduction and The Regulation Of Steroid Hormentioning

confidence: 82%

Polybrominated Biphenyl and Diphenylether Flame Retardants: Analysis, Toxicity, and Environmental Occurrence

Pijnenburg

Everts

Boer³

et al. 1995

Reviews of Environmental Contamination and Toxicology

121

View full text Add to dashboard Cite

Effects of polybrominated biphenyls on metabolism of testosterone by rat hepatic microsomes

Cited by 15 publications

References 22 publications

Exposure to polybrominated biphenyl (PBB) associates with genome-wide DNA methylation differences in peripheral blood

Exposure to polybrominated biphenyl (PBB) associates with genome-wide DNA methylation differences in peripheral blood

Maternal Exposure to a Brominated Flame Retardant and Genitourinary Conditions in Male Offspring

Polybrominated Biphenyl and Diphenylether Flame Retardants: Analysis, Toxicity, and Environmental Occurrence

Contact Info

Product

Resources

About