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REACTIVE OXYGEN SPECIES IN WHOLE BLOOD, BLOOD PLASMA AND BREAST MILK: VALIDATION OF A POTENTIAL MARKER OF EXPOSURE AND EFFECT
Citation:
HEIDENFELDER, B., E. P. HINES, E. R. SVENDSEN, E. E. HUDGENS, J. P. INMON, J. E. GALLAGHER, S. E. FENTON, R. L. SAMS, G. E. HATCH, AND K. YEATTS. REACTIVE OXYGEN SPECIES IN WHOLE BLOOD, BLOOD PLASMA AND BREAST MILK: VALIDATION OF A POTENTIAL MARKER OF EXPOSURE AND EFFECT. Presented at American Association for Cancer Research, Washington, DC, April 01 - 05, 2006.
Description:
Reactive oxygen species (ROS) are recognized to contribute to the pathobiology of many diseases. We have applied a simple chemiluminescent (CL) probe to detect ROS in various biological fluids (plasma, whole blood, urine and breast milk) in an environmental arsenic drinking water study (n=192) and four on-site clinical studies of healthy and asthmatic individuals. As part of our on-site clinical evaluations, we obtained plasma ROS values in healthy adults (n=80), asthmatic adults (n=93 observations from 12 subjects), asthmatic children (n= 17) and new mothers (n= 47 observations from 34 subjects). We hypothesized that systemic measures of ROS could serve as surrogate markers of inflammation, exposure and/or health effects. Despite a significant association between toenail arsenic levels and drinking water concentrations (p<0.0001, r2=0.325, n=693), no relationship was observed between arsenic levels in drinking water or urine and plasma ROS levels. This finding is in contrast to studies by Wu et al (Environ Health Perspect 109:1011-1017, 2001), where plasma ROS levels were associated with internal dose measurements of arsenic using the same CL probe. ROS levels in our arsenic drinking water study were highly correlated with vitamin use and most particularly with ascorbate plasma levels (p < 0.001). Plasma ROS levels in asthmatic children were highly correlated with FEV1 (p=0.012, r2=0.348), and FVC (p=0.015, r2=0.336). PMA-induced whole blood ROS levels were associated with the number of neutrophils per mL of blood in asthmatic children (p<0.001, r2=0.757), and with asthma severity score in asthmatic adults (p=0.02, r2=0.428). Putative modulators of ROS in the asthma clinical studies (uric acid and ascorbate) were also highly correlated with plasma ROS (p<0.01). Repeat measures of ROS in blood (n= 93) taken from 12 asthmatic adults indicate that ROS levels are remarkably consistent over a period of 13 weeks. Urinary levels of ROS from normal individuals (n=80) were not above background levels. In contrast, breast milk ROS levels were 1.8-fold higher than plasma levels taken from the same mother (t test, p<0.0001). In conclusion, a simple CL assay appears to be a valid probe for detecting ROS in blood and breast milk samples. While no association was observed between drinking water arsenic level and blood plasma ROS levels, two modulators of ROS appear to influence the magnitude of ROS levels. The association of a systemic measure of ROS with well established lung function measures is of interest. Ongoing clinical studies with controlled exposures to varied environmental pollutants that incorporate multiple markers of exposure and effects will assist in providing the evidence needed to further validate the usefulness of this CL probe in healthy and compromised individuals. These findings do not necessarily represent EPA policy.