The modulation of rat liver carcinogenesis by perfluorooctanoic acid, a peroxisome proliferator

Abdellatif, Awad G; Préat, Véronique; Taper, Henryk; Roberfroid, Marcel

doi:10.1016/0041-008x(91)90257-f

Cited by 75 publications

(34 citation statements)

References 24 publications

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“…For example, PFOA and PFDA are both mitogens (Chen et al, 1994). However, only PFOA was shown to induce tumors in Wistar rats using the biphasic and triphasic experimental protocols (Abdellatif et al, 1991), but PFDA failed to induce tumors in Sprague-Dawley rats using the biphasic protocol (Borges et al, 1993b). Effects of peroxisome proliferators are known to be strain-sensitive (Cattley and Preston, 1995), which could explain why PFOA caused tumors in Wistar rats and PFDA did not cause tumors in Sprague-Dawley rats.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of gap junctional intercellular communication by perfluorinated fatty acids is dependent on the chain length of the fluorinated tail

et al. 1998

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Perfluorinated fatty acids (PFFAs), such as perfluorooctanoic acid (PFOA) and perfluorodecanoic acid (PFDA), are known peroxisome proliferators and hepatocarcinogens. A causal link between an increase in the oxidative stress by peroxisomes and tumor promotion has been proposed to explain the hepatocarcinogenicity of PFOA and PFDA. However, the down-regulation of gap junctional intercellular communication (GJIC) has also been linked to the tumorpromoting properties of many carcinogens. Therefore, the effect of PFFAs on GJIC in WB-rat liver epithelial cells was determined. The chain length of the PFFAs tested for an effect on GJIC ranged from 2 to 10, 16 and 18 carbons. Carbon lengths of 7 to 10 inhibited GJIC in a dose-response fashion, whereas carbon lengths of 2 to 5, 16 and 18 did not appreciably inhibit GJIC. Inhibition occurred within 15 min and was reversible, with total recovery from inhibition occurring within 30 min after the removal of the compound from the growth medium. This short time of inhibition suggests that GJIC was modified at the post-translational level. Also, this short time period was not long enough for peroxisome proliferation. The post-translational modification of the gap junction proteins was not a consequence of altered phosphorylation as determined by Western blot analysis. Perfluorooctanesulfonic acid also inhibited GJIC in a dose-response fashion similar to PFDA, indicating that the determining factor of inhibition was probably the fluorinated tail, which required 7-10 carbons. Our results suggest that PFFAs could potentially act as hepatocarcinogens at the level of gap junctions in addition to or instead of through peroxisome proliferation.

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Section: Discussionmentioning

confidence: 99%

Inhibition of gap junctional intercellular communication by perfluorinated fatty acids is dependent on the chain length of the fluorinated tail

et al. 1998

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“…Prostate cancer mortality [11] Liver tumors, pancreatic acinar cell tumors, Leydig cell tumors [79] Hepatotoxicities Slight increases in total cholesterol, lowdensity lipoprotein, very low-density lipoprotein, gamma glutamyl aminotransferase, and aspartate aminotransferase [77] Hepatomegaly accompanied by mitochondrial proliferation, no peroxisome proliferation [85] Peroxisome proliferation, increased hepatocyte hypertrophy, increased labeling index [83] Developmental toxicities…”

Section: Pfoa Carcinogenicitymentioning

confidence: 99%

“…Hepatotoxicity and molecular targets of PFOA and PFOS Although these chemicals were found to be carcinogens for rodents [79,80], they were not genotoxic in umu tests [81]. It should be further investigated whether the hepatocarcinogenic potencies are in proportion to the degrees of induction of peroxisome proliferator-activated receptoralpha (PPARa), to which these chemicals bind as ligands [82].…”

Section: Pfoa Carcinogenicitymentioning

confidence: 99%

Environmental and biological monitoring of persistent fluorinated compounds in Japan and their toxicities

Harada

2008

Environ Health Prev Med

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Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) comprise a class of per- and poly-fluorinated compounds that have been detected in the environment as well as in humans. The aim of this review is to summarize several monitoring studies in Japan and characterize the toxicokinetics of these compounds. We found that the levels of contamination by these compounds had unique patterns in Japan. The levels of PFOA in serum from inhabitants of the Kansai region were higher than those of other regions. The PFOA levels in air and water samples from the Kansai region were also relatively high. The estimated intakes from these routes partly explain the differences in the serum levels. The toxicokinetics of these compounds have been investigated. Serum samples from male participants had significantly higher geometric means for PFOS and PFOA compared to samples from female participants. This sex-related difference was partly simulated by menstrual blood loss. There are large interspecies differences in the excretion pathways of these compounds. The serum clearances of PFOA via urine were 300-1,000-fold lower in humans than in Wistar rats and Japanese macaques. On the other hand, the biliary excretion of these compounds was comparable in rats and humans, and the long half-lives in humans may be attributable to the low levels of urinary excretion and high biliary reabsorption rates. These findings suggest that qualitative differences in the excretion routes exist between humans and other species. For risk assessment of these compounds, further information regarding sources of exposure and their toxicokinetics is needed.

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“…In rats, PFOA is a peroxisome proliferator activated receptor (PPAR) agonist causing liver toxicity (12,13) with hepatomegaly and hepatic necrosis, and biochemical effects characteristic of PPAR agonists (14). PFOA promotes liver carcinogenesis in rats (15), and causes Leydig-cell testicular tumors and acinar cell pancreatic tumors (16,17), through non-genotoxic mechanisms (18,19) with questionable human relevance. The human half-life of PFOA was between four and five years for retirees with previous heavy occupational exposure (20), much longer than in laboratory animals.…”

Section: Introductionmentioning

confidence: 99%

Community Exposure to Perfluorooctanoate: Relationships Between Serum Concentrations and Exposure Sources

Emmett

Shofer

Zhang

et al. 2006

Journal of Occupational and Environmental Medicine

320

300

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Objective-To determine serum [PFOA] in residents near a fluoropolymer production facility: the contributions from air, water and occupational exposures, personal and dietary habits, and relationships to age and gender.Methods-Questionnaire and serum PFOA measurements in a stratified random sample and volunteers residing in locations with the same residential water supply but with higher and lower potential air PFOA exposure. [PFOA] greatly exceeded general population medians. Occupational exposure from production processes using PFOA and residential water had additive effects, no other occupations contributed. Serum [PFOA] depended on the source of residential drinking water, and not potential air exposure. For public water users the best-fit model included age, tap water drinks per day, servings of home-grown fruit and vegetables, and carbon filter use. Results-SerumConclusions-Residential water source was the primary determinant of serum [PFOA].

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The modulation of rat liver carcinogenesis by perfluorooctanoic acid, a peroxisome proliferator

Cited by 75 publications

References 24 publications

Inhibition of gap junctional intercellular communication by perfluorinated fatty acids is dependent on the chain length of the fluorinated tail

Inhibition of gap junctional intercellular communication by perfluorinated fatty acids is dependent on the chain length of the fluorinated tail

Environmental and biological monitoring of persistent fluorinated compounds in Japan and their toxicities

Community Exposure to Perfluorooctanoate: Relationships Between Serum Concentrations and Exposure Sources

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