8-oxo-2--deoxyadenosine and Neoplasms

Findings from epidemiologic studies have been important in evaluating risk of exposure to many contaminants in drinking water. In the case of bromate, a byproduct of ozone disinfection of water, it is unlikely that observational studies of populations exposed to bromate in drinking water will be as revealing as studies of other contaminants, unless risks are much higher than predicted from laboratory studies of rodents. Occupational exposure to bromate has occurred in the flour milling and baking industries, as well as in chemical production of potassium bromate, used as a flour additive. The feasibility of a cohort study of bromate-exposed workers should be evaluated by studying the conditions and levels of exposure in these occupational settings. Bromate exposure causes oxidative damage to guanine bases of DNA, producing 8-hydroxy-guanine (8-OH-Gua), which is excised by 8-oxoguanosine glycosylase (OGG1) and excreted in the urine. Polymorphic variants of OGG1 in human populations have been associated with elevated cancer risk. 8-OH-Gua and 8-hydroxy-deoxyguanosine (8-OHdG) have been used as biomarkers of oxidative damage in many human studies, and it would be feasible to employ these indicators in controlled clinical experimental settings to see if exposure to bromate in water at levels close to the maximum contaminant level influences urinary levels of excretion, and if so, to help quantify the level of oxidative damage. Such a study could fill an important data gap by providing human data to help estimate the carcinogenic risk from this exposure.

Topics: Animals; Bromates; Case-Control Studies; Cohort Studies; Deoxyadenosines; DNA Damage; DNA Repair; Environmental Exposure; Feasibility Studies; Humans; Neoplasms; Occupational Exposure; Oxidative Stress; Rats; Research Design; Risk

Urinary 8-hydroxy-2'-deoxyguanosine (8OHdG) is an excellent marker of oxidative DNA damage. Until now, urinary 8OHdG has been measured by high-performance liquid chromatography with electrochemical detection. A simple and sensitive method for the analysis of urinary 8OHdG by capillary electrophoresis with end-column amperometric detection has been developed in our laboratory. A single-step solid-phase extraction procedure was optimized and used for extracting 8OHdG from human urine. To improve the sensitivity of this method, a new focusing technique based on a dynamic pH junction was used. The limit of detection was 20 nM (signal-to-noise ratio S/N = 3), the linear range was 50 nM-10 microM, and the correlation coefficient was better than 0.999. The relative standard deviation (RSD) was found to be 0.57% for migration time, and 4.79% for peak current. To show the usefulness of the method, the urinary concentration of 8OHdG in nine healthy persons and ten cancer patients was determined. The urinary concentration of 8OHdG in cancer patients was significantly higher than that in healthy persons.

Topics: Biomarkers; Case-Control Studies; Deoxyadenosines; DNA Damage; Electronics; Electrophoresis, Capillary; Female; Humans; Male; Neoplasms; Reproducibility of Results