Urinary 8-Hydroxy-2'-Deoxyguanosine as a Biomaker of Oxidative DNA Damage in Workers Exposed to Fine Particulates

Jee Young Kim; Sutapa Mukherjee; Long Ngo; David C. Christiani


Environ Health Perspect. 2004;112(6) 

In This Article

Abstract and Introduction

Residual oil fly ash (ROFA) is a chemically complex mixture of compounds, including metals that are potentially carcinogenic because of their ability to cause oxidative injury. In this study, we investigated the association between exposure to particulate matter with an aerodynamic mass median diameter ≤ 2.5 µm (PM2.5) and oxidative DNA damage and repair, as indicated by urinary 8-hydroxy-2´-deoxyguanosine (8-OHdG) concentrations, in a group of boilermakers exposed to ROFA and metal fumes. Twenty workers (50% smokers) were monitored for 5 days during an overhaul of oil-fired boilers. The median occupational PM2.5 8-hr time-weighted average was 0.44 mg/m3 (25th-75th percentile, 0.29-0.76). The mean ± SE creatinine-adjusted 8-OHdG levels were 13.26 ± 1.04 µg/g in urine samples collected pre-workshift and 15.22 ± 0.99 µg/g in the post-workshift samples. The urinary 8-OHdG levels were significantly greater in the post-workshift samples than in the pre-workshift samples (p = 0.02), after adjusting for urinary cotinine levels, chronic bronchitis status, and age. Linear mixed models indicated a significant exposure-response association between PM2.5 exposure and urinary 8-OHdG levels (p = 0.03). Each 1-mg/m3 incremental increase in PM2.5 exposure was associated with an increase of 1.67 µg/g (95% confidence interval, 0.21-3.14) in 8-OHdG levels. PM2.5 vanadium, manganese, nickel, and lead exposures also were positively associated with 8-OHdG levels (p ≤ 0.05). This study suggests that a relatively young and healthy cohort of boilermakers may experience an increased risk of developing oxidative DNA injury after exposure to high levels of metal-containing particulate matter.

Residual oil fly ash (ROFA) is a particulate air pollutant generated from the combustion of fuel oil. The chemical composition of ROFA includes sulfates, silicates, carbon- and nitrogen-containing compounds, and metals (Ghio et al. 2002). Of particular interest is the significant presence of bioavailable transition metals in ROFA, including vanadium, iron, and nickel and, to a lesser extent, chromium, manganese, and copper (Huffman et al. 2000). Exposure to ROFA, specifically the soluble metal component, has been shown to induce acute lung injury and airway inflammation in both animals and humans (Costa and Dreher 1997; Dreher et al. 1997; Gavett et al. 1997; Ghio et al. 2002; Hauser et al. 1995a, 1995b; Williams 1952; Woodin et al. 1998, 2000).

The carcinogenicity of ROFA itself has not been studied widely; however, several of the metals present in ROFA have been found to be carcinogenic (Hayes 1997; Nemery 1990). Occupational exposures to nickel and chromium were associated with an excess risk of lung and nasal cancer (Andersen et al. 1996; Anttila et al. 1998; Gibb et al. 2000). A recent study by the U.S. National Toxicology Program indicated that chronic inhalation exposure to vanadium pentoxide also might be carcinogenic, as evidenced by the increased incidence of alveolar/bronchiolar neoplasms in mice (Ress et al. 2003).

Although the carcinogenicity of certain metals has been recognized, the mechanism leading to the development of cancer is unclear. A possible mechanism is the induction of oxidative DNA damage by reactive oxygen species (ROS) (Hartwig 2000; Knaapen et al. 2002). Transition metals serve as catalysts in the generation of ROS through a Fenton-like chemical reaction (Pritchard et al. 1996). In addition to inducing oxidative DNA damage, metals may enhance further their carcinogenicity by interfering with DNA repair processes (Hartwig 2000).

The urinary excretion of 8-hydroxy-2´-deoxyguanosine (8-OHdG) often has been used as a biomarker to assess the extent of repair of ROS-induced DNA damage in both the clinical and occupational setting (Erhola et al. 1997; Honda et al. 2000; Lagorio et al. 1994; Pilger et al. 2000; Tagesson et al. 1993; Toraason et al. 2001). 8-OHdG is formed from a hydroxyl radical attack at the C-8 position of deoxyguanosine in DNA (Kasai et al. 1986). In a study of patients with small-cell carcinoma of the lung, elevated urinary 8-OHdG concentrations were observed compared with those of control subjects (Erhola et al. 1997). In workers exposed occupationally to benzene, a known carcinogen, a dose-response relationship was found between personal exposure to benzene and urinary 8-OHdG concentrations (Lagorio et al. 1994). Exposed workers in the asbestos, rubber, and azo-dye industries also were found to have significantly higher urinary 8-OHdG levels than those of nonexposed workers (Tagesson et al. 1993).

In this study, we investigated the association between personal exposure to fine particulate matter with an aerodynamic mass median diameter ≤ 2.5 µm (PM2.5) and oxidative DNA damage and repair, as indicated by urinary 8-OHdG levels, in a group of boilermakers performing maintenance and repairs on oil-fired boilers. The boilermakers were monitored over 5 consecutive workdays using a repeated-measures study design. Chemical analysis of the particulate sample was performed to determine exposure to the following six metal components of ROFA and metal fumes: vanadium, chromium, manganese, nickel, copper, and lead. Previous studies have shown that exposure to ROFA is associated with oxidative lung injury in animals; therefore, we hypothesized that increased exposure to fine particulates of ROFA would be associated with elevated urinary 8-OHdG levels in the boilermakers.