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.
Faux
S P
SP
School of Biochemistry, University of Birmingham, Edgbaston, UK.
Francis
J E
JE
Smith
A G
AG
Chipman
J K
JK
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001140:Aroclors / Q000008:administration & dosage*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D002273:Carcinogens / Q000008:administration & dosage*; D020111:Chlorodiphenyl (54% Chlorine); D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis; D004032:Diet; D007505:Iron-Dextran Complex / Q000008:administration & dosage*; D008099:Liver / Q000737:chemistry* / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000737:chemistry*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010084:Oxidation-Reduction; D011166:Porphyrins / Q000032:analysis
D001140:Aroclors; D002273:Carcinogens; D011166:Porphyrins; D020111:Chlorodiphenyl (54% Chlorine); D000080242:8-Hydroxy-2'-Deoxyguanosine; D007505:Iron-Dextran Complex; D001189:Aryl Hydrocarbon Hydroxylases; D003849:Deoxyguanosine