Lipid and DNA oxidative damage in experimentally induced hepatic porphyria in C57BL/10ScSn mice.
Patients with porphyria cutanea tarda (PCT) develop hepatocellular carcinoma as a late consequence. Pre-loading of C57BL/10ScSn mice with iron greatly sensitizes them to the induction of hepatic porphyria caused by hexachlorobenzene (HCB). HCB will also cause liver tumors in experimental animals. Elevated liver iron stores are implicated in the development of some human liver cancers in connection with its known catalytic role in generation of highly reactive activated oxygen species. The aim of this study was to determine the lipid and DNA oxidative damage in iron and HCB-induced porphyric mice. C57BL/10ScSn mice received i.p. injections of dextran sulfate (control), iron (Imferon) or combined iron and HCB. 6 weeks after treatment plasma ALT levels and hepatic free iron, porphyrin, lipid peroxides and 8-hydroxyguanosine (8-OHdG) levels were analyzed. Hepatic porphyrin level was significantly (p < 0.001) increased following combined iron/HCB treatment as compared to control mice. The level of lipid peroxides increased 9-fold (p = 0.001) and 35-fold (p < 0.001) after iron and iron/HCB treatment respectively, whereas the level of 8-OHdG was increased 2.5-fold (p = 0.002) and 7.5-fold (p < 0.001) after iron and iron/HCB treatment respectively as compared to control mice. The authors conclude that iron overload in conjugation with HCB induce lipid and DNA oxidative damage in C57BL/10ScSn mice. DNA oxidative damage may be important in the early events of hepatic carcinogenesis in experimental porphyria.
Horváth
M E
ME
Second Department of Medicine, Semmelweis University Medical School, Budapest, Hungary. vdlooij@oncol.hu
Faux
S P
SP
Blázovics
A
A
Fehér
J
J
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D004249:DNA Damage / Q000502:physiology*; D004195:Disease Models, Animal; D006432:Hemochromatosis / Q000139:chemically induced / Q000473:pathology*; D006581:Hexachlorobenzene / Q000633:toxicity; D007505:Iron-Dextran Complex / Q000633:toxicity; D015227:Lipid Peroxidation / Q000502:physiology*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017119:Porphyria Cutanea Tarda / Q000139:chemically induced / Q000473:pathology*; D017094:Porphyrias, Hepatic / Q000139:chemically induced / Q000473:pathology*
D006581:Hexachlorobenzene; D007505:Iron-Dextran Complex