Induction of 8-hydroxydeoxyguanosine in Ah-responsive mouse liver by iron and Aroclor 1254.

Treatment of Ah-responsive C57BL/10ScSn mice with iron greatly sensitizes them to induction of hepatic porphyria and tumour formation by the polychlorinated biphenyl mixture Aroclor 1254. In the present studies, male C57BL/10ScSn mice received a single dose of iron-dextran (600 mg Fe/kg) and were fed a diet containing 0.01% Aroclor 1254 for 1, 3 and 5 weeks. By use of HPLC with electrochemical detection, 8-hydroxydeoxyguanosine (8-OHdG) was then measured in liver DNA as a marker for oxidative damage. Treatments with iron or Aroclor alone did not result in a significant increase in 8-OHdG except at 3 weeks following iron treatment. At 1 and 3 weeks 8-OHdG levels were induced approximately 3- and 5-fold above control groups respectively in iron- and Aroclor-treated animals. Although there was an apparent 5- to 10-fold increase in the level of 8-OHdG at 5 weeks, this was partially attributed to the in vitro effects of porphyrins, levels of which were massively elevated in liver at this time point. The iron/Aroclor-induced synergistic elevation of 8-OHdG at 1 and 3 weeks was concluded to be due to in vivo damage, thus suggesting the importance of DNA oxidation in the early events of carcinogenesis in this system.