Concentrations of urinary 8-hydroxy-2′-deoxyguanosine and 8-isoprostane in women exposed to woodsmoke in a cookstove intervention study in San Marcos, Peru
Introduction
The use of solid fuels occurs mostly in the developing world where wood and crop residues are employed by households for cooking and heating (Smith and Mehta, 2003). These fuels are often used in unvented or poorly designed stoves which create high levels of household air pollution (Rehfuess et al., 2006). Biomass combustion in the indoor environment is considered to be probably carcinogenic for humans (IARC, 2010). Although numerous pollutants including carbon monoxide, polycyclic aromatic hydrocarbons, formaldehyde and benzene are produced from biomass combustion, particulate matter (PM) is considered the best indicator of smoke exposure (Naeher et al., 2007, Perez-Padilla et al., 2010).
Mounting evidence points to the mutagenic, genotoxic and cytotoxic properties of biomass smoke, particularly for woodsmoke particulate matter (Danielsen et al., 2009). One toxicological mechanism by which PM has been shown to induce health effects, in in-vitro studies involving human cells or cell lines, is through the pathway of oxidative stress (Danielsen et al., 2009). Oxidative stress can cause damage to deoxyribonucleic acid (DNA) through the production of 8-hydroxylated guanine species such as 8-hydroxy-2′-deoxyguanosine (8-OHdG) (Arnett et al., 2005). Another toxicological effect of PM observed in in-vitro studies, specifically of woodsmoke PM, involves the generation of reactive oxygen species (ROS) such as perioxides that can react with the lipids of cell membrane. A common stable product of ROS-induced lipid peroxidation is 8-isoprostaglandin F2α (8-isoprostane) (Danielsen et al., 2009). Hence, both 8-OHdG and 8-isoprostane are known markers of oxidative stress (Barregard et al., 2006, Loft et al., 1992).
8-Isoprostane is a prostaglandin (PG)-F2-like compound belonging to the F2 isoprostane class that is produced in vivo by the free radical-catalyzed peroxidation of arachidonic acid (Montuschi et al., 1999). On the other hand 8-OHdG is an oxidized nucleoside of DNA and it is considered as the most frequently detected and studied DNA lesion (Wu et al., 2004). 8-OHdG is excreted during the repair of DNA damage (Wu et al., 2004). Measurements of these compounds have been performed in biologic fluid, particularly in urine and can provide quantitative indices of oxidative stress (Montuschi et al., 1999). Aside from experimental studies where the effect of woodsmoke on oxidative stress has been studied (Barregard et al., 2006, Barregard et al., 2008), the literature is scant on studies of biomass smoke exposure and resulting health effects, particularly regarding women in the developing world who cook with biomass fuels. Given the daily HAP exposure experienced by these women over a lifetime, there is the need to better understand the effect of woodsmoke exposure on oxidative stress in this vulnerable population.
In this study, we examined the concentrations of oxidative stress biomarkers of women exposed to woodsmoke. Study subjects from San Marcos, Cajarmarca Region, Peru, used wood as fuel for cooking and high PM levels have been measured among this population (Hartinger et al., 2013). Based on earlier studies among this population which did not reveal statistically significant differences in PM2.5 and CO measurements (Commodore et al., 2013, Hartinger et al., 2013), the primary focus of this study was to assess the association of urinary oxidative stress with biomass smoke exposure among control and intervention stove users as a combined population. Therefore this study examined the use of biomarkers in investigating oxidative stress, which plays a role in many diseases and in natural aging.
The aims of this study were (1) to determine whether increased exposure to biomass cookstove smoke was associated with increased urinary levels of 8-OHdG and 8-isoprostane among control and intervention subjects and (2) to investigate the factors that are associated with urinary 8-OHdG and 8-isoprostane concentrations among study subjects. We assessed woodsmoke exposure with personal and kitchen measurements of particulate matter and carbon monoxide. Woodsmoke exposure was also assessed with urinary hydroxylated polycyclic aromatic hydrocarbons (hydroxy-PAH), metabolites of PAHs generated through incomplete combustion (Li et al., 2012).
Section snippets
Study design and study homes
From June to August 2009, a cross sectional study was conducted within the framework of a community based randomized control trial (c-RCT) by the Instituto de Investigación Nutricional (IIN) and the Swiss Tropical and Public Health Institute (Commodore et al., 2013, Hartinger et al., 2013). The aim of the parent study was to evaluate an integrated home-based environmental intervention package (IHIP) against childhood diarrhea and respiratory infections (Hartinger et al., 2011). The May–August
Household characteristics
Household specific information is presented according to stove type (Table 1). Intervention households used OPTIMA FL-I (n = 22) or OPTIMA FL-II (n = 17) stoves and control households used NGO stoves (n = 7), traditional stoves (n = 29) or stoves that were self-improved by the household (n = 9). Subjects' mean ages were similar among all study households (Table 1). Mean cooking time for study subjects was above 3 h (Table 1). Eucalipto (Eucalyptus sp.) was the most popular wood types used as cooking fuel
Discussion
It has been observed in in-vitro and human experimental studies that oxidative stress, in response to wood smoke, may play an important role in airway and alveolar epithelium injury (Barregard et al., 2006, Barregard et al., 2008, Danielsen et al., 2009, Danielsen et al., 2011). 8-Isoprostane is produced in vivo by the free radical-catalyzed peroxidation of arachidonic acid (Montuschi et al., 1999) while 8-OHdG is an oxidized nucleoside of DNA and the most frequently detected molecule of DNA
Conclusion
We characterized urinary 8-OHdG and 8-isoprostane among intervention and control households in San Marcos, Cajamarca Region, Peru. Although both oxidative stress biomarkers did not differ significantly between control and intervention stove users, 8-OHdG levels appear to be elevated among our study subjects when compared to values of urinary 8-OHdG reported in healthy women in the scientific literature from the developed world. It is important to realize that reductions in wood smoke exposure
Funding source
This exposure assessment was made possible by NIH Research Grant #5-D43TW005746-04 funded by the Fogarty International Center, National Institutes on Environmental Health Services, National Institute for Occupational Safety and Health, and the Agency for Toxic Substances and Disease Registry. Additional funding for urinary biomarker analysis was from the University of Georgia (UGA) Graduate School and the UGA Interdisciplinary Toxicology Program. This work was also supported by the UBS Optimus
Acknowledgments
Sincere appreciation goes to:
Study subjects who allowed us to sample in their homes; the IIN staff in Lima who helped with logistical issues of storing and transporting samples; Hector Verastegui for compiling the data set for the randomized control trial; field coordinator, Selenne Flores, the field workers and volunteers, who enabled the successful campaign of this study; Adam Gray who helped with pre- and post-field work data analysis and management and Christopher Fitzgerald who conducted
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