Activity of Benzo[a]pyrene and Its Hydroxylated Metabolites in an Estrogen Receptor-alpha Reporter Gene Assay

Charles, Grantley D.

doi:10.1093/toxsci/55.2.320

Cited by 162 publications

(110 citation statements)

References 35 publications

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“…Polychlorinated biphenyls are converted to hydroxylated metabolites in animals, and some hydroxylated polychlorinated biphenyls show estrogenic and/or antithyroid hormonal activity (Connor et al 1997;Garner et al 1999;Korach et al 1988). Further, methoxychlor, trans-stilbene, benzophenone, and benzo [a]pyrene are proestrogens that require metabolic activation by liver microsomal mixed-function oxidase in animals (Charles et al 2000;Fertuck et al 2001;Gaido et al 1999;Nakagawa and Suzuki 2002;Sugihara et al 2000). In contrast, the estrogen screening Weights of the reproductive organs of rats were expressed.…”

Section: Discussionmentioning

confidence: 99%

Antiandrogenic activity and metabolism of the organophosphorus pesticide fenthion and related compounds.

Kawa

Suzuki

Ohta

et al. 2003

Environ Health Perspect

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We investigated the endocrine-disrupting actions of the organophosphorus pesticide fenthion and related compounds and the influence of metabolic transformation on the activities of these compounds. Fenthion acted as an antagonist of the androgenic activity of dihydrotestosterone (10(-7)M) in the concentration range of 10(-6)-10(-4)M in an androgen-responsive element-luciferase reporter-responsive assay using NIH3T3 cells. The antiandrogenic activity of fenthion was similar in magnitude to that of flutamide. Fenthion also tested positive in the Hershberger assay using castrated male rats. Marked estrogenic and antiestrogenic activities of fenthion and related compounds were not observed in MCF-7 cells. When fenthion was incubated with rat liver microsomes in the presence of NADPH, the antiandrogenic activity markedly decreased, and fenthion sulfoxide was detected as a major metabolite. The oxidase activity toward fenthion was exhibited by cytochrome P450 and flavin-containing monooxygenase. Fenthion sulfoxide was negative in the screening test for antiandrogens, as was fenthion sulfone. However, when fenthion sulfoxide was incubated with liver cytosol in the presence of 2-hydroxypyrimidine, an electron donor of aldehyde oxidase, the extract of the incubation mixture exhibited antiandrogenic activity. In this case, fenthion was detected as a major metabolite of the sulfoxide. Metabolic interconversion between fenthion and fenthion sulfoxide in the body seems to maintain the antiandrogenic activity.

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Section: Discussionmentioning

confidence: 99%

Antiandrogenic activity and metabolism of the organophosphorus pesticide fenthion and related compounds.

Kawa

Suzuki

Ohta

et al. 2003

Environ Health Perspect

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“…PAHs were the major chemical group found in this fraction (Wang et al, 2003). Several PAHs, including benzo[α]pyrene (BaP) and benz [α]anthracene (BaA), or their oxygenated derivatives, have been shown to act as estrogenic compounds in ER-regulated receptor gene assays (Chaeles et al, 2000). Recently, several other PAHs, including fluorine, fluoranthene, pyrene, chrysene, phenanthrene and anthracene, were found to act as very weak inducers of ER-mediated activity in MCF-7 cells (Vondráček et al, 2002).…”

Section: Estrogenic Activity Of Sediment Samplesmentioning

confidence: 99%

Measurement of estrogenic activity in sediments from Haihe and Dagu River, China

Song

Jiang

et al. 2006

Environment International

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Sediments from two rivers in China, the Haihe and Dagu Rivers, were examined for estrogenic activity using an estrogen receptor (ER)-mediated in vitro bioassay system. ER-active compounds were isolated from sediments by Soxhlet extraction, and the crude extracts were fractionated using a florisil column into three fractions. The estrogenic activity of each extract was detected by measuring luciferase activity in the human breast cancer cell line MCF-7 transfected with a luciferase receptor gene. Significant estrogenic activity was observed in each total extract. The 17β-estradiol equivalents (E2-EQs) ranged from 8.24 to 95.28 ng E2 g − 1 dw. As a result, the relative estrogenic potencies of three fractions in this study descended in the order of Fraction 3 N Fraction 2 N Fraction 1. The results of the bioassay analysis indicated the heavy pollution status of these sites with estrogenic contaminants. In this study, five selected chemicals, the natural estrogens 17β-estradiol (E2) and estrone (E1), and the xeno-estrogens 4-octylphenol (OP), 4-nonylphenol (NP), and Bisphenol A (BPA) were also analyzed using the in vitro bioassay. The estrogenic activity of these chemicals were E2 N E1 N NP N OP N BPA.

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“…The Th2 shift in the group with the highest dose of B[a]P through the estrogenic activity of this PAH was also possible as estrogen alone may have this effect (Huber et al, 1999;Salem, 2004). Several recent studies have reported that some PAHs, including B[a]P can activate estrogen receptors, either directly or indirectly by producing estrogenic metabolites (Charles et al, 2000;Fertuck et al, 2001;Pliskova et al, 2005).…”

Section: Discussionmentioning

confidence: 96%

Effects of postnatal exposure to benzo[a]pyrene on the immunity of immature rats

Matiašovic¹,

Levá²,

Mašková³

et al. 2008

Vet. Med. - Czech

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ABSTRACT:To determine the effect of benzo [a]pyrene (B[a]P) on the developing immune system of immature rats, newborn animals received different concentrations (0.1, 1.0 and 10.0 mg/kg/day) of B[a]P in the first 14 days after birth. These rats were euthanised on day 23 of the experiment and it was found that the decreasing numbers of erythrocytes were in direct correlation to the dose of B[a]P. In subject animals, the overall counts of T cells in the spleen and the mitogenic activity increased. A decrease in the production of both IFN-γ and IL-4 (measured at the mRNA level) as well as the decreasing IFN-γ/IL-4 ratio in rat splenocytes were dependent on the dose of B[a]P. From this we may deduce that exposure to B[a]P in immature animals may modulate the immune response to infection and/or vaccination. Keywords: polycyclic aromatic hydrocarbons; immunity; IFN-γ; IL-4; cytokinesPolycyclic aromatic hydrocarbons (PAHs) are mostly anthropogenic in origin and are released both as a result of incomplete combustion in coal, oil, gasoline and wood and in consequence of some other pyrolytic processes (Motelay-Massei et al., 2007). Benzo [a]pyrene (B[a]P) is widely used as a prototypical PAH which exhibits significant genotoxicity and negative effects on different components of the immune system. The impact of B[a]P on the immune system varies from reduced humoral immunity to increased T cell mitogenic activity (Davila et al., 1996;Burchiel and Luster, 2001;Burchiel et al., 2004 (Harper et al., 1996).In earlier studies, it was the toxic effects of B[a]P that were mainly described and decreases in humoral and cell-mediated immunity were documented (Ward et al., 1984;Dean et al., 1986). The differences in the sensitivity of humans and rodents to varying doses of B[a]P were also described and the observation that humans were 10-100 times more sensitive to toxic effects of B[a]P than rodents was made (Davila et al., 1996). Depending on their doses, different fractions of the reconstituted PAH mixture show different effect on the humoral and cell-mediated immunity in mouse splenocytes (Harper et al., 1996). Interestingly, in more recent studies, signs of a possible adjuvant effect of PAHs or DE were shown. For example, increasing in vitro mitogenic activity of mouse spleen T cells in the presence of 1 µM B[a]P was documented (Burchiel et al., 2004). Also Fujimaki et al. (2001) found an increasing production of IFN-γ but not IL-4 and IL-5 by splenocytes in mice exposed to DE. In contrast, the work of Diaz-Sanchez et al. (1997) showed a decreased expression of mRNA for Th1-type cytokines (IFN-γ and IL-2) but an elevated expression for other cytokines (IL-4, 5, 6, 10, and 13) in human cells isolated from nasal lavages after stimulation by ragweed allergens and exposure to DE particles. The mechanism of this effect is not clear, but seems to be complex due to possible interaction between PAH metabolites and different lymphocyte signalling pathways such as the aryl hydrocarbon

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Activity of Benzo[a]pyrene and Its Hydroxylated Metabolites in an Estrogen Receptor-alpha Reporter Gene Assay

Cited by 162 publications

References 35 publications

Antiandrogenic activity and metabolism of the organophosphorus pesticide fenthion and related compounds.

Antiandrogenic activity and metabolism of the organophosphorus pesticide fenthion and related compounds.

Measurement of estrogenic activity in sediments from Haihe and Dagu River, China

Effects of postnatal exposure to benzo[a]pyrene on the immunity of immature rats

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