Hypolipidaemic hepatic peroxisome proliferators form a novel class of chemical carcinogens

Reddy, Janardan K.; Azarnoff, Daniel L.; Hignite, Charles E.

doi:10.1038/283397a0

Cited by 804 publications

(255 citation statements)

References 12 publications

Supporting

Mentioning

252

Contrasting

Order By: Relevance

“…Circulating concentrations of steroid hormones such as estrogen, (E 2 ), progesterone (P) and androgens have been hypothesized to influence cancer risk, including breast, ovarian, testicular and prostate cancers (Lukanova and Kaaks, 2005;Folkerd and Dowsett, 2010). Chronic exposure to the ligand of PPAR induces development of cancers in livers of both rats and mice (Reddy et al, 1980(Reddy et al, , 1976Rao and Reddy 1987;Pyper et al, 2010), whereas elevated concentrations of glucocorticoids in blood might lead to insulin resistance and diabetes (Chrousos and Kino, 2009;Longui and Faria, 2009;Barnes, 2010). EDCs with retinoic acid-like activities can interfere with embryonic development and differentiation of secondary characteristics of males (Bowles et al, 2006;Bowles and Koopman, 2007).…”

Section: Receptor-mediated Reporter Assaysmentioning

confidence: 99%

Biological analysis of endocrine-disrupting chemicals in animal meats from the Pearl River Delta, China

Law

Wei

Zhang

et al. 2011

J Expo Sci Environ Epidemiol

View full text Add to dashboard Cite

Endocrine disrupting chemicals (EDCs) consist of a diverse group of industrial chemicals and pharmacological agents. The use of instrumental analyses as the first screening tool might not be cost-effective to identify the existence of enormous numbers of chemical contaminants in environments. Also, knowledge of the concentration of individual residues is difficult to use to evaluate biological impacts of contaminants to wildlife and humans. The primary objective of the present study was to develop and to test the feasibility of using a battery of exposure biomarkers for the rapid-screening of various endocrine disrupting activities present in food. The measurement of the EDC-elicited activities involved various (i) receptor-mediated responses, including androgenic, estrogenic, dioxin-like, glucocorticoid-like, progesterone-like, peroxisome proliferator-like and retinoid-like as well as (ii) the non-receptor mediated responses through modulation of cellular reactive oxygen species (ROS) and ATP content. Samples of both local and imported pork, beef and chicken as well as freshwater and seawater fishes were collected. Extracts of different foods exhibited various dioxin-like and ''hormonal'' activities. Fish and chicken skin were found to be the major source of exogenous ''hormonal'' and dioxin-like substances in diets. Extracts of beef and pork contained lesser potencies of hormonally-active agents. Our data suggest that the proposed EDC-screening platform may be useful in a risk assessment for the routine monitoring of EDCs in foods. Continuous monitoring and research is warranted to assess the physiological consequences of the consumption.

show abstract

Section: Receptor-mediated Reporter Assaysmentioning

confidence: 99%

Biological analysis of endocrine-disrupting chemicals in animal meats from the Pearl River Delta, China

Law

Wei

Zhang

et al. 2011

J Expo Sci Environ Epidemiol

View full text Add to dashboard Cite

show abstract

“…46 PPARa mediates the activity of these compounds on peroxisome proliferation and the long-term consequences on hepatocellular carcinoma development as showed by the lack of response of the PPARa null-mutant mice. 47,48 This involvement of PPARs in the action of phthalate is consistent with the in vitro activation of PPARa, but also PPARb and PPARg using transactivation assays and intact cellular systems with endogenous receptors and target genes.…”

Section: Pparc and Phthalates: Stepping In With The Definition Of A Smentioning

confidence: 99%

Interference of pollutants with PPARs: endocrine disruption meets metabolism

2008

View full text Add to dashboard Cite

The concept of endocrine disruption emerged over a decade ago with the observation that several natural or industrial compounds can interfere with estrogen and androgen signaling, and thereby affect both male and female reproductive functions. Since then, many endocrine-disrupting chemicals (EDCs) have been identified and the concept has been broadened to receptors regulating other aspects of endocrine pathways. In that context, interference of EDCs with receptors regulating metabolism has been proposed as a factor that could contribute to metabolic diseases such as obesity and diabetes. We review recent studies showing that several pollutants, including phthalates and organotins, interfere with PPAR (peroxisome proliferator-activated receptors) nuclear receptors and may thereby affect metabolic homeostasis. Particular emphasis is given on the mechanisms of action of these compounds. However, unlike what has been suspected, we provide evidence from mouse models suggesting that in utero exposure to the phthalate ester di-ethyl-hexyl-phthalate most likely does not predispose to obesity. Collectively, these studies define a subclass of EDCs that perturb metabolic signaling and that we propose to define as metabolic disruptors.

show abstract

“…Peroxisome proliferators are a class of structurally diverse compounds that cause cancer in rodents by a non-genotoxic mechanism [1][2][3]. The high potential for human exposure and the known rodent carcinogenicity of these compounds has been the cause for intense debate for several decades regarding their potential adverse health effects in people [4].…”

Section: Introductionmentioning

confidence: 99%

Sustained formation of α-(4-pyridyl-1-oxide)-N-tert-butylnitrone radical adducts in mouse liver by peroxisome proliferators is dependent upon peroxisome proliferator-activated receptor-α, but not NADPH oxidase

Woods

Burns

Maki

et al. 2007

Free Radical Biology and Medicine

View full text Add to dashboard Cite

Reactive oxygen species are thought to be crucial for peroxisome proliferator-induced liver carcinogenesis. Free radicals have been shown to mediate the production of mitogenic cytokines by Kupffer cells and cause DNA damage in rodent liver. Previous in vivo experiments demonstrated that acute administration of the peroxisome proliferator di-(2-ethylhexyl) phthalate (DEHP) led to an increase in production of α-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN) radical adducts in liver, an event that was dependent on Kupffer cell NADPH oxidase, but not peroxisome proliferator activated receptor (PPAR)α. Here, we hypothesized that continuous treatment with peroxisome proliferators will cause a sustained formation in POBN radical adducts in liver. Mice were fed diets containing either 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio acetic acid (WY-14,643, 0.05% w/w), or DEHP (0.6% w/w) for up to three weeks. Liver-derived radical production was assessed in bile samples by measuring POBN-radical adducts using electron spin resonance. Our data indicate that WY-14,643 causes a sustained increase in POBN radical adducts in mouse liver and that this effect is greater than that of DEHP. To understand the molecular source of these radical species, NADPH oxidase-deficient (p47 phox -null) and PPARα-null mice were examined after treatment with WY-14,643. No increase in radicals was observed in PPARα-null mice that were treated with WY-14,643 for 3 weeks, while the response in p47 phox -nulls was similar to that of wild-type mice. These results show that PPARα, not NADPH oxidase, is critical for a sustained increase in POBN radical production caused by peroxisome proliferators in rodent liver. Therefore, peroxisome proliferator-induced POBN radical production in Kupffer cells may be limited to an acute response to these compounds in mouse liver.

show abstract

Hypolipidaemic hepatic peroxisome proliferators form a novel class of chemical carcinogens

Cited by 804 publications

References 12 publications

Biological analysis of endocrine-disrupting chemicals in animal meats from the Pearl River Delta, China

Biological analysis of endocrine-disrupting chemicals in animal meats from the Pearl River Delta, China

Interference of pollutants with PPARs: endocrine disruption meets metabolism

Sustained formation of α-(4-pyridyl-1-oxide)-N-tert-butylnitrone radical adducts in mouse liver by peroxisome proliferators is dependent upon peroxisome proliferator-activated receptor-α, but not NADPH oxidase

Contact Info

Product

Resources

About