Polychlorinated Dibenzo-p-dioxins and Polychlorinated Dibenzofurans: The Risks to Human Health. A Review

Skene, S.A.; Dewhurst, Ian Crawford; Greenberg, Morris

doi:10.1177/096032718900800301

Cited by 108 publications

(47 citation statements)

References 160 publications

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“…Many environmental toxicants (Safe, 2001;Skene et al, 1989) such as polycyclic aromatic hydrocarbons, generated from incomplete pyrolysis of carbon sources, and halogenated aromatic hydrocarbons, which are formed during industrial chlorination processes and as byproducts of combustion, activate AhR. Halogenated aromatic hydrocarbons comprise three families of related compounds: polychlorinated dibenzo-p-dioxins (CDDs-75 congeners), polychlorinated dibenzofurans (CDFs-135 congeners) and polychlorinated biophenyls (PCBs-209 congeners), for which AhR is the primary mediator of their toxicity.…”

Section: Introductionmentioning

confidence: 99%

Increased arylhydrocarbon receptor expression offers a potential therapeutic target for pancreatic cancer

et al. 2002

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The arylhydrocarbon receptor (AhR) was initially identified as a member of the adaptive metabolic and toxic response pathway to polycyclic aromatic hydrocarbons and to halogenated dibenzo-p-dioxins and dibenzofurans. In the present study, we sought to determine the functional significance of the AhR pathway in pancreatic carcinogenesis. AhR expression was analysed by Northern blotting. The exact site of AhR expression was analysed by in situ hybridization and immunohistochemistry. The effects of TCDD and four selective AhR agonists on pancreatic cancer cell lines were investigated by growth assays, apoptosis assays, and induction of the cyclin-dependent kinase inhibitor p21. There was strong AhR mRNA expression in 14 out of 15 pancreatic cancer samples, weak expression in chronic pancreatitis tissues, and faint expression in all normal pancreata. In pancreatic cancer tissues, AhR mRNA and protein expression were localized in the cytoplasm of pancreatic cancer cells. TCDD and the four AhR agonists inhibited pancreatic cancer cell growth in a dose-dependent manner, and decreased anchorage-independent cell growth. DAPI staining did not reveal nuclear fragmentation and CYP1A1 and was not induced by TCDD and AhR agonists. In contrast, TCDD and AhR agonists induced the expression of the cyclindependent kinase inhibitor p21. In conclusion, the relatively non-toxic AhR agonists caused growth inhibition in pancreatic cancer cells with high AhR expression levels via cell cycle arrest. In addition, almost all human pancreatic cancer tissues expressed this receptor at high levels, suggesting that these or related compounds may play a role in the therapy of pancreatic cancer in the future.

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Section: Introductionmentioning

confidence: 99%

Increased arylhydrocarbon receptor expression offers a potential therapeutic target for pancreatic cancer

et al. 2002

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“…Chemicals that are known EDs include dioxins, which are a class of persistent polychlorinated aromatic hydrocarbons, and some of the most potent environmental contaminants that induce a wide spectrum of toxic responses in both animals and humans [2]. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a well-known dioxin which is formed as a byproduct during the commercial production of 2,4,5-trichlorophenoxyacetic acid, a herbicide utilized extensively as a defoliant [22] and which is currently released into the environment primarily through emissions from the incineration of municipal and chemical wastes, in exhaust from automobiles using leaded gasoline, and from the improper disposal of certain chlorinated chemical wastes.…”

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confidence: 99%

Dose Paternal Exposure to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) affect the Sex Ratio of Offspring?

Ishihara

Warita

Tanida

et al. 2007

The Journal of Veterinary Medical Science

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ABSTRACT. In 1976, men who were exposed to the highest concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) after an explosion at a chemical plant near Seveso, Italy, produced more girls than boys. However, few studies have examined the possibility that the exposure of laboratory animals to TCDD, especially that of males, could lead to a lower male/female sex ratio. The aim of this study was to investigate whether direct paternal exposure to TCDD affects the sex ratio of offspring using a relatively large-scale experimental design. Male ICR mice (n=120) were randomly assigned to three, one of which served as a vehicle control, the other two were administered TCDD orally with an initial loading dose of 2 or 2,000 ng TCDD/kg, followed by a weekly maintenance dose of 0.4 (T2/0.4 group) or 400 (T2000/400 group) ng/kg prior to mating. The major organs of each mouse were weighed and histopathologically and immunohistologically investigated, and the sex ratio of offspring [males/(males + females) × 100] was calculated in each dam. There were no significant effects on organ weights, or on the structure of the testis and epididymis between the control and TCDD-exposed males, but TCDD administration produced a significantly lower proportion of male offspring from T2000/400-exposed sires despite no alteration in litter size (Control: 53.1 ± 1.7; T2/0.4: 48.8 ± 2.5; T2000/400: 46.2 ± 2.1). In addition, we further divided the T2000/400 group into 3 subgroups based on the proportion of CYP1A1-immunoreactive areas in the liver; there was a significant correlation between sex ratio and CYP1A1 immunoreactivity. Thus, the present study confirms that direct paternal exposure to TCDD might be associated with an alteration in the sex ratio of offspring. Possible mechanisms through which TCDD might decrease the fertility potential of Ybearing gametes before conception are discussed. KEY WORDS: CYP1A1, paternal exposure, Seveso data, sex ratio of offspring, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

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“…PCDD, PCDF, and PCB produce a wide spectrum of toxic effects in animals including body weight loss, immunotoxicity, thymic atrophy, hepatotoxicity, teratogenicity, carcinogenicity, and reproductive toxicity (8,9). Furthermore, they can alter thyroid hormone status in laboratory animals.…”

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Effects of Dioxins and Polychlorinated Biphenyls on Thyroid Hormone Status of Pregnant Women and Their Infants

et al. 1994

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Dioxins [polychlorinated dibenzo-p-dioxins (PCDD), dibenzofurans (PCDF)] and polychlorinated biphenyls (PCB) are potentially hazardous compounds. Animal studies have demonstrated that PCDD, PCDF, and PCB can alter thyroid hormone homeostasis. We investigated thyroid hormone levels in 105 mother-infant pairs. To estimate maternal and infant exposure, four nonplanar PCB congeners were measured in maternal plasma during the last month of pregnancy and in umbilical cord plasma. Seventeen PCDD and PCDF congeners, three planar PCB congeners, and 23 nonplanar PCB congeners were measured in human milk. Higher PCDD, PCDF, and PCB levels in human milk, expressed as toxic equivalents, correlated significantly with lower plasma levels of maternal total triiodothyronine and total thyroxine, and with higher plasma levels of TSH in the infants in the 2nd wk and 3rd mo after birth. Infants exposed to higher toxic equivalents levels had also lower plasma free thyroxine and total thy-PCDD and PCDF, summarized as dioxins, are tricyclic aromatic compounds. Because the number of chlorine atoms can vary between one and eight, there are potentially 75 different PCDD and 135 PCDF congeners. They are mainly formed as by-products during the synthesis of organochlorine chemicals and during the combustion of municipal and hazardous waste (1). PCB are a compilation of 209 possible congeners with different chlorine substitutions. Because of their unique physical properties and chemical stability, mixtures were used for diverse

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Polychlorinated Dibenzo-p-dioxins and Polychlorinated Dibenzofurans: The Risks to Human Health. A Review

Cited by 108 publications

References 160 publications

Increased arylhydrocarbon receptor expression offers a potential therapeutic target for pancreatic cancer

Increased arylhydrocarbon receptor expression offers a potential therapeutic target for pancreatic cancer

Dose Paternal Exposure to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) affect the Sex Ratio of Offspring?

Effects of Dioxins and Polychlorinated Biphenyls on Thyroid Hormone Status of Pregnant Women and Their Infants

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