Urinary trans,trans-Muconic Acid as an Indicator of Exposure to Benzene in Cigarette Smokers1

Epidemiological studies have shown an association between cigarette smoking and increased risk of myeloid leukemia in smokers. In evaluating this link it is important to note that cigarette smoke contains benzene, among other carcinogens. Since chronic benzene exposure causes acute myeloid leukemia in humans, we aimed to determine the uptake and metabolic activation of benzene from cigarette smoke in smokers by measuring the levels of the urinary benzene metabolite, tnans,tnans-muconic acid (t,t-MA). The method used involved a clean-up procedure, followed by high-performance liquid chromatography with UV detection. The levels of urinary t,t-MA ranged from 0.02 to 1.3 mg/g creatinine, resulting in a mean of 0.29 ± 0.04 mg/g creatinine in 42 male smokers, and corresponding values in nonsmokers ranged from “nondetectable” to 0.52 mg/g creatinine with an average of 0.09 ± 0.02 mg/g creatinine. In the current study, the levels of t,t-MA in smokers were about 3 times higher than those in nonsmokers (P = 0.0001), and a significant correlation between concentration of t,t-MA and levels of cotinine in smokers was observed (n 0.55; P = 0.0001; 95% confidence interval, 0.300.93), suggesting that urinary t,t-MA can be utilized as a biochemical marker to quantitate benzene exposure due to cigarette smoking.