Association of persistent peroxisome proliferation and oxidative injury with hepatocarcinogenicity in female F-344 rats fed di(2-ethylhexyl)phthalate for 2 years.
Female F-344 rats were fed a diet containing up to 1.2% di(2-ethylhexyl)phthalate (DEHP) for 2 years, which previously resulted in hepatocarcinogenesis under bioassay conditions. Peroxisome proliferation, decreased glutathione peroxidase activity, and lipofuscin accumulation were all associated with prolonged feeding of 1.2% DEHP and induction of hepatic neoplasia. These results establish a potential role for persistent peroxisome proliferation and oxidative injury in the hepatocarcinogenicity of dietary DEHP. Increased hepatocellular proliferation and hepatomegaly were not detected. DEHP feeding did not increase the volume density of basophilic or ATPase-deficient foci of altered hepatocytes, suggesting that these lesions are not suitable indicators of DEHP carcinogenesis.
Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709.
R C
RC
Cattley
J G
JG
Conway
J A
JA
Popp
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D005260:Female; D008062:Lipofuscin / Q000032:analysis; D008099:Liver / Q000187:drug effects*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008830:Microbodies / Q000187:drug effects*; D010084:Oxidation-Reduction; D010795:Phthalic Acids / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D008062:Lipofuscin; D010795:Phthalic Acids; D004051:Diethylhexyl Phthalate