Affiliations: Garyounis Faculty of Medicine, Pharmacology
Department, Benghazi, Lybia | Benha Faculty of Medicine, Medical Biochemistry
Department, Egypt | Mansoura Faculty of Medicine, Forensic Medicine and
Clinical Toxicology Department, Egypt | Ecole de Pharmacie, Bruxelles, Belgium | Garyounis Faculty of Medicine, Pathology Department,
Benghazi, Lybia
Note: [] Address for correspondence: Ahmad Hisham Al-tonsy, 10 Metwaly
Noor Str., From Tayaran Str., Beside Dr. Abou El-azayem Hospital, Nasr City,
Cairo, Egypt. Tel.: +2 02 4026748 or +2 0105251867; E-mail:
[email protected]
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.
