Immunosuppressive activities of polychlorinated biphenyls in C57BL/6N mice: Structure-activity relationships as Ah receptor agonists and partial antagonists

Davis, D.; Safe, Stephen

doi:10.1016/0300-483x(90)90072-o

Cited by 104 publications

(30 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: Discussionmentioning

confidence: 99%

“…Previous studies demonstrate that unlike Aroclor 1254, a complete displacement of [ 3 H]TCDD from the Ah receptor was not observed in 2,2',4,4',5,5'-hexaCB competitive binding assays; moreover, [ l25 I 2 ]2,2',5,5'-tetrachloro-4,4'-diiodobiphenyl did not bind directly to the Ah receptor (Davis and Safe, 1990). These results suggest that the antagonism observed for 2,2',4,4',5,5'-hexaCB may occur by mechanisms other than through the Ah receptor (Davis and Safe, 1990). A recent study by De Jongh et al (1995) has shown that the concentration of TCDD in the liver (% dose/ g tissue) was increased in the animals cotreated with TCDD and 2,2',4,4',5,5'-hexaCB compared to the animals treated with TCDD alone.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Inhibition of 3,3′,4,4′,5-Pentachlorobiphenyl-Induced Chicken Embryotoxicity by 2,2′,4,4′,5,5′-Hexachlorobiphenyl

Zhao¹,

MAYURA²,

KOCUREK³

et al. 1997

Toxicol Sci

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Inhibition of 3,3′,4,4′,5-Pentachlorobiphenyl-Induced Chicken Embryotoxicity by 2,2′,4,4′,5,5′-Hexachlorobiphenyl

Zhao¹,

MAYURA²,

KOCUREK³

et al. 1997

Toxicol Sci

View full text Add to dashboard Cite

“…ortho-substituted biphenyls, display no or weak affinity for the Ah-receptor [31]. Some of the toxicity observed for PCBs involves reproductive toxicity [31], immunotoxicity [34], neurotoxicity [35] as well as induction of hepatic xenobiotic-metabolizing enzymes [36]. PCB exposure is also associated with a modest decrease in maternal and umbilical cord serum arachidonic acid concentrations [37].…”

Section: Introductionmentioning

confidence: 99%

Polychlorinated biphenyls induce arachidonic acid release in human platelets in a tamoxifen sensitive manner via activation of group IVA cytosolic phospholipase A2-α

Forsell

Olsson

Andersson

et al. 2005

Biochemical Pharmacology

View full text Add to dashboard Cite

Polychlorinated biphenyls (PCBs) are stable compounds commonly found in nature as environmental pollutants. PCBs can affect the endocrine function of hormones such as steroid-hormones. Also, PCBs are known to be inducers of arachidonic acid release in various cells. We report, here, the effects of PCBs on eicosanoid formation, arachidonic acid release and cytosolic phospholipase A 2 -α(cPLA 2 -α) activation in human platelets. Ortho-substituted PCBs induced a time and dosedependent release of arachidonic acid and the concomitant formation of 12(S)-hydroxy-5,8-cis-10-trans-14-cis-eicosatetraenoic acid (12-HETE) and 12(S)-hydroxy-5-cis-8,10-transheptadecatrienoic acid (12-HHT) in human platelets. The release of arachidonic acid and the formation of 12-HETE was completely blocked by the cPLA 2 -α inhibitors AACOCF 3 or pyrrolidine-1. PCB-treatment of platelets demonstrated that the cPLA 2 -α protein as well as PLA 2 activity translocated to the membrane fraction, independent of a rise in intracellular Ca 2+ . Furthermore, electrophoretic gel mobility shift analysis of cPLA 2 -α on SDS-PAGE demonstrated a PCB-dependent phosphorylation of cPLA 2 -α. The effects of 17β-estradiol and two structurally unrelated anti-estrogens, nafoxidin and tamoxifen on PCB-induced arachidonic acid release in platelets were also investigated. Both nafoxidin and tamoxifen inhibited PCB-induced arachidonic acid release as well as 12-HETE and 12-HHT formation. Interestingly, platelets incubated with PCBs did not aggregate despite the fact that robust release of arachidonic acid was observed. In summary, these results demonstrate that certain PCBs induce activation of cPLA 2 -α independent of a rise in intracellular calcium and a robust release of arachidonic acid release with resulting eicosanoid formation in human platelets.

show abstract

“…TCDD has deleterious effects on human as well as wildlife health. Wasting (cachexia), thymic involution, tumor promotion, hepatotoxicity, developmental toxicity, and immunosuppression are a few of the pathological effects of TCDD (14,15). TCDD is also known to induce oxidative stress, production of superoxide and peroxide radicals, and DNA singlestrand breaks (16)(17)(18).…”

mentioning

confidence: 99%

Dioxin-mediated tumor progression through activation of mitochondria-to-nucleus stress signaling

Biswas

Srinivasan

Anandatheerthavarada

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

Immunosuppressive activities of polychlorinated biphenyls in C57BL/6N mice: Structure-activity relationships as Ah receptor agonists and partial antagonists

Cited by 104 publications

References 30 publications

Inhibition of 3,3′,4,4′,5-Pentachlorobiphenyl-Induced Chicken Embryotoxicity by 2,2′,4,4′,5,5′-Hexachlorobiphenyl

Inhibition of 3,3′,4,4′,5-Pentachlorobiphenyl-Induced Chicken Embryotoxicity by 2,2′,4,4′,5,5′-Hexachlorobiphenyl

Polychlorinated biphenyls induce arachidonic acid release in human platelets in a tamoxifen sensitive manner via activation of group IVA cytosolic phospholipase A2-α

Dioxin-mediated tumor progression through activation of mitochondria-to-nucleus stress signaling

Contact Info

Product

Resources

About