Age-related radical-induced DNA damage is linked to prostate cancer

We measured concentrations and ratios of mutagenic (8-OH) lesions to putati vely nonmutagenic formamidopyrimidine (Fapy) lesions of adenine (Ade) and g uanine (Gua) to elucidate radical (. OH)-induced changes in DNA of normal, normal from cancer, and cancer tissues of the prostate. The relationship be tween the lesions was expressed using the mathematical model log(10)[(8-OH- Ade + 8-OH-Gua)/(FapyAde + FapyGua)]. Logistic regression analysis of the l og ratios for DNA of normal and cancer tissues discriminated between the tw o tissue groups with high sensitivity and specificity. Correlation analysis of log ratios for normal prostates revealed a highly significant increase in the proportion of mutagenic base lesions with age. Data from correlation analysis of the log ratios for normal tissues from cancer were consistent with an age-dependent, dose-response relationship. The slopes for both corr elations intersected at similar to 61 years, an age when prostate cancer in cidence is known to rise sharply. The age-related increase in the proportio n of . OH-induced mutagenic base lesions is likely a significant factor in prostate cancer development.