Effect of the peroxisome proliferator perfluorodecanoic acid on the promotion of two-stage hepatocarcinogenesis in rats

Subacute exposure to N-ethyl perfluorooctanesulfonamidoethanol results in the formation of perfluorooctanesulfonate and alters superoxide dismutase activity in female rats

“…Taken together, the similarity of the effect of PFOS-based chemicals on the growth rate and liver weight suggests a common underlying cause for both effects. As expected based on earlier studies (Borges et al, 1993; Chen et al, 1994), the liver weight in the ciprofibrate group was significantly increased compared to controls due to peroxisome proliferation. Despite the changes in organ weights, histopathological evaluation did not reveal any pathological changes in the liver or uterus of the N-EtFOSE treatment group.…”

“…As shown in Figure 2, PCA of the 1 H NMR data revealed no differences between corn oil and N-EtFOSE treated animals, despite the fact that N-EtFOSE treatment caused general toxicity (i.e., decrease in the growth rate and increased liver weight; Table 1) at the dose investigated. Ciprofibrate, a well investigated peroxisome proliferator (Borges et al, 1993; Chen et al, 1994; Glauert et al, 1992; Huang et al, 1994; Wilson et al, 1995), did not affect metabolomic markers typically associated with exposure to other peroxisome proliferators, such as amino acids (Sheikh et al, 2007) or, possibly, tryptophan-NAD + pathway metabolites (Connor et al, 2004; Delaney et al, 2005; Sheikh et al, 2007). However, ciprofibrate treatment resulted in slightly, but significantly higher phosphatidylcholine and/or sphingomyelin levels compared to corn oil- and N-EtFOSE-treated animals.…”

“…The study was designed to resemble previous studies investigating the effect of perfluorochemicals, such as perfluorodecanoic acid, on peroxisome proliferation and oxidative stress (Borges et al, 1993; Chen et al, 1994; Glauert et al, 1992; Huang et al, 1994; Wilson et al, 1995). Twenty six sexually mature female Sprague-Dawley rats (10 weeks, 220±20 g; Harlan, Indianapolis, IN) were placed in cages in a controlled environment, maintained at 22°C with a 12 hour light–dark cycle, and with food and water ad libitum.…”

“…Initially, changes in systemic biomarkers of oxidative stress, mitochondrial dysfunction and peroxisome proliferation were assessed in comparison to ciprofibrate using a NMR metabolomic approach. Ciprofibrate was selected because its hepatotoxicity has been studied in parallel with other perfluorochemicals (Borges et al, 1993; Chen et al, 1994; Glauert et al, 1992; Huang et al, 1994; Wilson et al, 1995). In addition, the activities of peroxisomal acyl Co-A oxidase (AOX) and selected antioxidant enzymes were measured in the liver, a known target organ of perfluorinated compounds.…”

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

“…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.…”