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ACCUMULATION OF M1DG DNA ADDUCTS AFTER CHRONIC EXPOSURE TO PCBS, BUT NOT FROM ACUTE EXPOSURE TO DIOXIN-LIKE COMPOUNDS
JEONG, Y. C., N. J. WALKER, D. BURGIN, L. S. BIRNBAUM, AND J. A. SWENBERG. ACCUMULATION OF M1DG DNA ADDUCTS AFTER CHRONIC EXPOSURE TO PCBS, BUT NOT FROM ACUTE EXPOSURE TO DIOXIN-LIKE COMPOUNDS . Free Radical Biology and Medicine. Elsevier Science Ltd, New York, NY, 45(5):585-591, (2008).
This paper describes a highly specific new marker for oxidative stress. This paper also demonstrates that chronic exposure to PCBs causes this effect.
ABSTRACT: Oxidative DNA damage is one of the key events leading to mutation and cancer. The present study examined the accumulation of M1dG DNA adducts, 3-(2’-deoxy-β-D-erythro-pentofuranosyl)-pyrimido[1,2-a]-purin-10(3H)-one, after single or yearly exposure to polyhalogenated aromatic hydrocarbons (PHAH) in order to test the role of oxidative DNA damage in PHAH carcinogenicity. The effect of PHAH exposure on the number of M1dG adducts was explored initially in female mice exposed to a single dose of either TCDD or a PHAH mixture. This study demonstrated that a single exposure to PHAH had no significant effect on the number of M1dG adducts compared to the corn oil control group. The role of M1dG adducts in PCB-induced carcinogenicity was further investigated in rats exposed for a year to PCB 153, PCB 126, or a mixture of the two. PCB 153 had no significant effect on M1dG adducts number in liver and brain tissues from the exposed rats compared to controls. However, high dose PCB 126 exposure resulted in M1dG adducts accumulation in the liver. More importantly, starting at low doses, co-administration of equal proportions of PCB 153 and PCB 126 resulted in dose-dependent increases in M1dG adducts accumulation in the liver. Interestingly, the result from co-administration of different amounts of PCB 153 with fixed amounts of PCB 126 demonstrated more M1dG adducts accumulation with higher doses of PCB 153. These results are consistent with the results from cancer bioassays that demonstrated a synergistic effect between PCB 126 and PCB 153 on tumor development. In summary, the results from the present study support the hypothesis that oxidative DNA damage plays a role in the carcinogenicity after long-term PCB exposure.