Expression of Base Excision DNA Repair Genes Is a Sensitive Biomarker for in Vivo Detection of Chemical-induced Chronic Oxidative Stress: Identification of the Molecular Source of Radicals Responsible for DNA Damage

Oxidative stress to DNA is recognized as one of the mechanisms for the carcinogenic effects of some environmental agents. Numerous studies have been conducted in an attempt to document the fact that chemical carcin-ogens that are thought to induce production of oxidants also cause the formation of oxidative DNA lesions. Although many DNA adducts con-tinue to be useful biomarkers of dose/effect, changes in gene expression have been proposed to be a practical novel tool for studying the role of chemically induced oxidative DNA damage. Here, we hypothesized that expression of base excision DNA repair genes is a sensitive biomarker for in vivo detection of chemically induced chronic oxidative stress. To test this hypothesis, mice were treated with a known rodent carcinogen and peroxisome proliferator, WY-14,643 (500 ppm, 1 month). A number of end points that are commonly used to assess oxidative DNA damage were considered. Our data demonstrate that no difference in 8-oxoguanine, th