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performed and additional urine samples have been archived for AMK and 8-Ohdg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.
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