MELATONIN AS A BIOMARKER OF OXIDATIVE STRESS IN HUMANS

（申请人描述）证据表明，

DESCRIPTION (Applicant's Description) Evidence suggests that the hormone, melatonin, may also be one of the body's most potent antioxidants. A metabolic product of melatonin's antioxidant reactions, N-acetyl-5-methoxykynuramine (AMK), is excreted in the urine as a different compound than its major urinary metabolite, 6-hydroxy melatonin sulfate (6-OHMS). Thus, urinary AMK excretion may serve as an indicator of the endogenous antioxidant activity of melatonin. In addition to its antioxidant properties, melatonin directly inhibits tumor growth, enhances the immune response and inhibits the release of hormones that are necessary for hormone-dependent of the relative amount AMK and 6-OHMS in urine may prove useful in future studies of the relationship between melatonin, oxidative stress, and human carcinogenesis. The objective of this pilot study is to test the hypothesis that AMK excretion is associated with oxidative DNA damage and repair by comparing urinary AMK levels with urinary, 8-hydroxy 2'-deoxyguanosine (8-OHdg). This hypothesis will be tested by comparing urinary AMK, 6-OHMS and 8-Ohdg levels in a population of 55 tobacco smokers and 55 nonsmokers. This study will take advantage of studies of melatonin in 400 individuals where 6-OHMS analyses have been performed and additional urine samples have been archived for AMK and 8-Ohdg analyses. The specific aims of this project are to: 1.) Assess oxidative DNA damage by measuring urinary 9-Ohdg in a group of smokers and nonsmokers; 2.) Determine the relationship between urinary melatonin metabolites (AMK and 6-OHMS) and oxidative DNA damage as measured by 8-OHdg; 3.) Characterize within and between subject variability in AMK, 6-OHMS and 8-OHdg excretion; 4.) Assess dose-response by comparing tobacco consumption with urinary AMK, 6-OHdg and 8-OHdg levels.