Short-term exposure to the peroxisome proliferators, perfluorooctanoic acid and perfluorodecanoic acid, causes significant increase of 8-hydroxydeoxyguanosine in liver DNA of rats.
To elucidate the relationship between peroxisome proliferation by perfluorinated compounds and oxidative DNA damage, perfluorooctanoic acid (PFOA), perfluorodecanoic acid (PFDA), perfluorobutyric acid (PFBA) and perfluorooctane (PFO) were administered to 6-week-old F-344 male rats. After a single intraperitoneal (i.p.) injection of PFOA, PFBA or PFO in corn oil at a dose of 100 mg/kg, significant increases of liver weight and 8-hydroxydeoxyguanosine (8-OH-dG) levels in liver DNA were observed in PFOA-treated rats. Oral administration of powdered diet containing 0.02% PFOA or 0.01% PFDA for 2 weeks resulted in significant increases of liver weight and 8-OH-dG levels in liver DNA in rats given both chemicals. On the other hand, no increase in 8-OH-dG levels in kidney DNA was found in either of the studies. Our results demonstrate that, as with other peroxisome proliferators (phthalic ester plasticizers and hypolipidemic drugs), PFOA and PFDA induced peroxisome proliferation also leads to organ specific oxidative DNA damage.
Takagi
A
A
Division of Toxicology, National Institute of Hygienic Sciences, Tokyo, Japan.
Sai
K
K
Umemura
T
T
Hasegawa
R
R
Kurokawa
Y
Y
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000284:Administration, Oral; D000818:Animals; D002210:Caprylates / Q000008:administration & dosage / Q000494:pharmacology*; D003652:Decanoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D005466:Fluorocarbons / Q000008:administration & dosage / Q000494:pharmacology*; D007668:Kidney / Q000033:anatomy & histology / Q000187:drug effects; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008830:Microbodies / Q000187:drug effects*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D012016:Reference Values
D002210:Caprylates; D003652:Decanoic Acids; D005466:Fluorocarbons; C036567:perfluorodecanoic acid; C033094:perfluorobutyric acid; D000080242:8-Hydroxy-2'-Deoxyguanosine; C023036:perfluorooctanoic acid; D003849:Deoxyguanosine