Lipid and DNA oxidative damage in experimentally induced hepatic porphyriain C57BL/10ScSn mice

Patients with porphyria cutanea tarda (PCT) develop hepatocellular carcinom a as a late consequence. Pre-loading of C57BL/10ScSn mice with iron greatly sensitizes them to the induction of hepatic porphyria caused by hexachloro benzene (HCB). HCB will also cause liver tumors in experimental animals. El evated liver iron stores are implicated in the development of some human li ver cancers in connection with its known catalytic role in generation of hi ghly reactive activated oxygen species. The aim of this study was to determ ine the lipid and DNA oxidative damage in iron and HCB-induced porphyric mi ce. C57BL/10ScSn mice received i.p. injections of dextran sulfate (control), ir on (Imferon) or combined iron and HCB. 6 weeks after treatment plasma ALT l evels and hepatic free iron, porphyrin, lipid peroxides and 8-hydroxyguanos ine (8-OHdG) levels were analyzed. Hepatic porphyrin level was significantly (p < 0.001) increased following c ombined 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 a nd iron/HCB treatment respectively, whereas the level of 8-OHdG was increas ed 2.5-fold (p = 0.002) and 7.5-fold (p < 0.001) after iron and iron/HCB tr eatment respectively as compared to control mice. The authors conclude that iron overload in conjugation with HCB induce lipi d and DNA oxidative damage in C57BL/10ScSn mice. DNA oxidative damage may b e important in the early events of hepatic carcinogenesis in experimental p orphyria.