A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Environmental Engineering and Management Inter-University Program on Environmental Toxicology, Technology and Management

Thesis (Ph.D.) - Asian Institute of Technology - Chulabhorn Research Institute - Mahidol University, 2008

Traffic related urban air pollution is a major environmental health problem in many large cities. These pollutants contain a variety of carcinogenic compounds including benzene. Children living in urban areas are exposed to benzene and other toxic pollutants simultaneously on a regular basis. Assessment of benzene exposure and oxidative DNA damage in schoolchildren in Bangkok compared with the rural schoolchildren was studied through the use of various biomarkers. Furthermore, the effect of genetic polymorphisms on biomarker levels was investigated. Benzene levels in ambient air at the roadside adjacent to Bangkok schools was 3.95-fold greater than that of rural school areas (Chonburi province) (17.75±2.23 ppb versus 4.49±0.59, P<0.001). Personal exposure to benzene in Bangkok schoolchildren was 3.04-fold higher than that in the rural schoolchildren (8.25±0.78 ppb versus 2.71±0.38, P< 0.001). Blood benzene and urinary benzene levels were significantly increased in the Bangkok schoolchildren. There was a significant increase of afternoon urinary muconic acid (MA) levels in Bangkok schoolchildren compared to rural schoolchildren (0.12±0.01 mg/c, creatinine versus 0.06±0.01; P<0.001). A significantly higher level of 8-hydroxy-2'deoxyguanosine (8-OHdG) in urine was found in Bangkok children than in the rural children (2.13±0.24 mol/mol creatinine versus 1.33±0.20, P<0.05, respectively). An increased level of 8-OHdG in urban schoolchildren compared to the rural group suggests that exposure to ambient air pollution in Bangkok may also contribute to oxidative damage to DNA. There was a significant correlation between individual benzene exposure level and blood benzene (rs=0.193, P<0.05), urinary benzene (rs=0.298, P<0.05), and urinary MA (rs=0.348, P<0.01). In addition, a significant correlation between urinary MA and 8-OHdG in urine (rs=0.07, P<0.05) was also found. CYP2E1 *1/*1, NQO1 *1/*2, GSTA1 *A/*A, GSTM1 *2/*2 and GSTT1 *1/ were prevalent genotypes observed in children in our study. Effects of benzene toxicity varies depend on benzene level in environment, duration of exposure. Gene encoding enzymes that involved in biotransformation of benzene may also modify biomarkers levels. However, among the studied polymorphisms of various xenobiotic metabolizing genes responsible for susceptibility to benzene toxicity, only the GSTM1 genotypes had a significant effect on urinary M A excretion (P<0.05). Schoolchildren who carried the GSTM1 *1/ genotype excreted more urinary MA than those with the GSTM1 *2/*2 genotype. Other genetic polymorphisms (CYP2E1, NQO1, GSTA1, and GSTT1) have no significant effect on blood and urinary benzene, MA and 8-OHdG. Our data indicates that children living in the areas of high traffic density, such as Bangkok are exposed to a higher level of benzene than those living in rural areas. Children who spent more time close to traffic-related sources may be more vulnerable to environmental health threats due to long-exposure term. Exposure to higher level of benzene in urban children may contribute to oxidative DNA damage, suggesting an increased health risk from traffic benzene emission