Results are consistent with previous reports that asphalt or coal-tar exposure can cause DNA damage. Urinary 8-epi-PGF remained relatively constant during the week for virtually all subjects, regardless of exposure indicating that neither asphalt nor coal-tar exposure induces an overt oxidative stress. A small, but statistically significant increase in 8OHdG was evident in end-of-week urine samples compared with start-of-week urine samples in roofers exposed to coal-tar. The increase in urinary 8OHdG coupled with the decrease in leukocyte 8-OHdG/dG, suggests that coal-tar exposure induces protective or repair mechanisms that result in reduced levels of steady-state oxidative-DNA damage.

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The absorption of calcium by segments of duodenum obtained from spontaneously hypertensive (SH) rats and normotensive Wistar-Kyoto (WKy) rats was measured before and after the development of hypertension. The systolic blood pressure (SBP) of 5-wk-old SH rats (116 +/- 4 Torr) was significantly elevated above that of age-matched WKy rats (103 +/- 3 Torr) but was not at a level generally considered to be hypertensive. Values obtained for calcium transport [ratio of serosal-to-mucosal fluid 45Ca2+ concn (S/M ratio)] from everted duodenal sacs were similar between the two groups at this age. At 12 wk of age, SH rats exhibited a SBP (153 +/- 4 Torr) well above that of WKy controls (127 +/- 3 Torr), and calcium S/M ratios for duodenal sacs were significantly greater than the WKy control values. Similarly, the in vivo uptake of calcium in duodenal segments was significantly elevated in 12-wk-old SH rats compared with WKy controls. The administration of vitamin D3 or its metabolite, 25-hydroxycholecalciferol, had no detectable effect on duodenal transport of calcium in 12-wk-old SH or WKy rats. By comparison, 1,25-dihydroxycholecalciferol produced a significant increase in duodenal calcium transport both in vitro and in vivo in WKy but not in SH rats. The results indicate a distinct abnormality in the transport of calcium in the duodenum of SH rats, suggesting that the decrease in duodenal uptake of calcium that normally occurs with maturation is slow to develop in this rat strain.

Increasing evidence suggests that noise-induced hearing loss may be prevented with antioxidant therapy. In order to appreciate treatment constraints, a biochemical marker(s) of reactive oxygen species (ROS)-induced damage is necessary. Without a marker, the timing of damage and biologically effective exposure(s) cannot be understood fully. This study examined the time course of ROS damage following noise exposure resulting in permanent threshold shift in a rat. Cochlea, brain, liver, serum and urine were analyzed. Oxidative DNA damage was assessed by measuring 8-hydroxy-2′-deoxyguanosine (8OHdG) by high performance liquid chromatography with electrochemical detection (HPLC-EC). Lipid peroxidation was measured via the thiobarbituric acid reactive substance’s (TBARS’s) colormetric assay for detection of aldehydes (e.g., malondialdehyde). Auditory brainstem response and distortion product otoacoustic emissions thresholds showed progressive elevation up to 3–8-h post-exposure, then notable recovery at 72 h, and some worsening at 672 h. 8OHdG/dG was significantly elevated in cochlea at 8-h post-exposure, and in the brain and liver at 72 h. TBARS were significantly elevated in serum at 72 h. This is the first evidence that oxidative DNA damage is present in cochlea following intense noise, and that the timing of damage corresponds to the timing of functional impairment.

To date, the 8-hydroxydeoxyguanosine (8OHdG) DNA adduct has been used as a biomarker in 11 occupational health studies examining the potential for ten different workplace exposures to cause oxidative DNA damage. Exposures examined include asbestos, azo-dyes, benzene, chromium, coal dust, glassworks, rubber manufacturing, styrene, toluene and environmental tobacco smoke (ETS). Experimental designs that applied 8OHdG as biomarker varied dramatically among the studies. For example, one study detected increased urinary excretion in retired workers with a history of exposure to mining dusts, while a study of workers exposed to benzene showed that the pattern of urinary excretion of 8OHdG varied over a 24h period following exposure. All but one study reported increased 8OHdG relative to controls, but in three cases the increases were not statistically significant. Only one study demonstrated a dose-response relationship between a chemical exposure (benzene) in the workplace and elevated 8OHdG. In most cases, exposure data were lacking and the elevated 8OHdG could only be considered to be associated with a generalized job category. Numerous animal and human studies have demonstrated an effect of tobacco smoke on 8OHdG, including a study of ETS in the workplace. In the majority of occupational studies, however, smoking was found not to be a confounding variable. 8OHdG levels tended to be higher in women than men as did the response to an occupational exposure and/or smoking. Two of three studies that stratified workers by age found it to be a confounder for the 8OHdG adduct, but the relationship between age and 8OHdG was non-linear. Only one study considered the impact of dietary supplements on 8OHdG levels in workers despite the fact that diet can have a marked effect on an individual's response to oxidative stress. It is premature to consider 8OHdG as biomarker that can be used for decision making or for regulatory purposes. Nonetheless, these studies demonstrate that with additional characterization of the role 8OHdG plays in the exposure-disease continuum it may well serve as a powerful biomonitoring toolin the future.