present in the steady-state. Increased 8-oxo-dG in carcinogenesis and disease As reviewed by Valavanidis et al. increased levels of 8-oxo-dG in a tissue can serve as a biomarker of oxidative stress. They also noted that increased levels of 8-oxo-dG are frequently found associated with carcinogenesis and disease. In the figure shown in this section, the colonic epithelium from a mouse on a normal diet has a low level of 8-oxo-dG in its colonic crypts (panel A). However, a mouse likely undergoing colonic tumorigenesis (due to deoxycholate added to its diet) has a high level of 8-oxo-dG in its colonic epithelium (panel B). Deoxycholate increases intracellular production of reactive oxygen resulting in increased oxidative stress, and this may contribute to tumorigenesis and carcinogenesis. Of 22 mice fed the diet supplemented with deoxycholate, 20 (91%) developed colonic tumors after 10 months on the diet, and the tumors in 10 of these mice (45% of mice) included an adenocarcinoma (cancer). Cooke et al. point out that a number of diseases, such as Alzheimer's disease and systemic lupus erythematosus, have elevated 8-oxo-dG but no increased carcinogenesis. Indirect role of oxidative damage in carcinogenesis Valavanidis et al. pointed out that oxidative DNA damage, such as 8-oxo-dG, may contribute to carcinogenesis by two mechanisms. The first mechanism involves modulation of gene expression, whereas the second is through the induction of mutations. Epigenetic alterations Epigenetic alteration, for instance by methylation of CpG islands in a promoter region of a gene, can repress expression of the gene (see DNA methylation in cancer). In general, epigenetic alteration can modulate gene expression. As reviewed by Bernstein and Bernstein, the repair of various types of DNA damages can, with low frequency, leave remnants of the different repair processes and thereby cause epigenetic alterations. 8-oxo-dG is primarily repaired by base excision repair (BER). Li et al. reviewed studies indicating that one or more BER proteins also participate(s) in epigenetic alterations involving DNA methylation, demethylation or reactions coupled to histone modification. Nishida et al. examined 8-oxo-dG levels and also evaluated promoter methylation of 11 tumor suppressor genes (TSGs) in 128 liver biopsy samples. These biopsies were taken from patients with chronic hepatitis C, a condition causing oxidative damages in the liver. Among 5 factors evaluated, only increased levels of 8-oxo-dG was highly correlated with promoter methylation of TSGs (p<0.0001). This promoter methylation could have reduced expression of these tumor suppressor genes and contributed