Peroxisomal Enzymes and 8‐Hydroxydeoxyguanosine in Rat Liver Treated with Perfluorooctanoic Acid

Abstract

Although peroxisome proliferators are considered non-genotoxic agents, most of them, nevertheless, were found to promote and/or induce, hepatocellular carcinoma (HCC) in rodents. The aim of the present study is, first, to investigate whether the peroxisome proliferator perfluorooctanoic acid (PFOA) possesses inherent liver cancer promoting activity, and second, to study the possible mechanisms involved. To acheive these aims two protocols have been applied, a biphasic protocol (initiation by diethyl-nitrozamine (DEN) 200 mg/kg i.p. followed by treatment with 0.005% or 0.02% perflourooctanoic acid (PFOA) for 14 and 25 weeks) and a triphasic initiation, selection-promotion (IS) protocol (initiation by giving 200 mg/kg DEN i.p. followed by a selection procedure for 2 weeks consisting of giving 0.03% 2-acetylaminofluorene (2-AAF) in diet). In the middle of this treatment a single oral dose of carbon tetrachloride (2.0 ml/kg) was given, followed by giving diet containg 0.015% of PFOA for 25 weeks. After applying both protocols, our results showed slight increase in the catalase activity while acyl CoA oxidase activity was markedly increased. Both experiments indicated that PFOA has a liver cancer promoting activity. Other groups of rats were given either basal diet or diet containing 0.02% PFOA. Five or nine weeks later they were sacrificed and the levels of 8-hydroxydeoxyguanosine in the isolated DNA were estimated. The data showed a slight nonetheless insignificant increase in 8-hydroxydeoxyguanosine. From the present data, it is concluded that PFOA is a true liver cancer promoter that may not require extensive initial DNA damage for its promoting activity.

PFAS Environmental Pollution and Antioxidant Responses: An Overview of the Impact on Human Field

“…Looking at previous studies in animal and cell models, in which the increased oxidative stress resulted as an important response to PFC exposure [183][184][185][186], the influence of low-level environmental PFC exposure on serum metabolome was studied in a cohort of 181 adult males individuals (males, in order to avoid the periodical female endocrine changes) from the general population was studied [187]. In particular, serum samples were investigated for different PFCs concentrations and metabolome changes.…”

Modeled Perfluorooctanoic Acid (PFOA) Exposure and Liver Function in a Mid-Ohio Valley Community

“…Large doses of PFOA are known to cause liver enlargement in rodents and non-human primates ( Butenhoff et al 2002 ; Lau et al 2007 ; Qazi et al 2010 ), and hepatocellular adenomas in rats ( Abdellatif et al 2003 ). These effects are at least partially mediated by activation of the peroxisome proliferator-activated receptor-alpha (PPAR-α), a major regulator of lipid metabolism in the liver, but also involve the activation of other nuclear receptors ( Bjork et al 2011 ; Elcombe et al 2010 ).…”

Investigation of the Effects of Perfluorooctanoic Acid (PFOA) and Perfluorooctane Sulfonate (PFOS) on Apoptosis and Cell Cycle in a Zebrafish (Danio rerio) Liver Cell Line

“…PFOA and PFOS can be found in the liver, serum and other tissues of humans and animals [ 12 ]. For rats chronic exposure to PFOA and PFOS is associated with tumor development in the liver, pancreas and testis [ 13 , 14 , 15 ]. Furthermore, PFOS has been reported to induce in vivo hepatocellular hypertrophy, lipid vacuolation, loss of body weight, and lower serum total cholesterol in monkeys [ 16 ].…”