Modification of the relationship between urinary 8-OHdG and hippuric acid concentration by GSTM1, GSTT1, and ALDH2 genotypes

Abstract

<jats:p> Urinary hippuric acid (HA) has been widely used as a biological marker of occupational exposure to toluene, although it is no longer valid for low levels of toluene exposure. Toluene exposure is known to induce oxidative DNA damage and the metabolism is affected by genetic polymorphisms of some metabolizing enzymes. Therefore, genetic polymorphisms of these metabolizing enzymes must be considered in the evaluation of oxidative stress caused by toluene exposure. We evaluated the relationship between urinary 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative DNA damage, and urinary HA in individuals without occupational exposure to toluene and characterized the possible roles of GSTM1, GSTT1, and aldehyde dehydrogenase 2 (ALDH2) genotypes in the relationships between these markers. In this study, we enrolled 92 healthy Koreans. Urinary HA and 8-OHdG levels were measured and the correlations between them were statistically tested according to the GSTM1, GSTT1, and ALDH2 genotypes. HA did not significantly correlate with urinary 8-OHdG in overall subjects. However, the correlation between them showed a statistical significance in individuals with GSTM1-null, GSTT1-null, and ALDH2 *2/*2 genotypes (r = 0.766, p &lt; 0.01). This study shows that the relationship between urinary HA and 8-OHdG concentration is modified by genetic polymorphisms of some metabolizing enzymes such as GSTM1, GSTT1, and ALDH2. </jats:p>

Association of metabolites of benzene and toluene with lipid profiles in Korean adults: Korean National Environmental Health Survey (2015–2017)

“…Individual sensitivity to benzene exposure may be influenced by nucleotide polymorphisms in NQO1, MPO, CYP2E1, GSTT1, and GSTM1 [ 57 , 58 ]. Genetic polymorphisms in ALDH2, CYP1A1, CYP2E1, GSTM1, and GSTT2 can affect their ability to metabolize toluene [ 59 , 60 ]. Fourth, the specificity of ttMA in assessing environmental exposure to benzene may have some limitations.…”

A case report of idiopathic environmental intolerance: A controversial and current issue

“…26,27 On the other hand, particular polymorphisms of the CYP2D6 gene give the carrier a slow metaboliser phenotype, which leads to increased blood concentrations of the same xenobiotics and the consequent oxidative stress. 28 It is known, moreover, that the null genotype of the GSTT1 gene predisposes to the accumulation of DNA-hippuric acid adducts 29 : This compound is a metabolite of many chemists with an aromatic structure, including some disinfectants, such as benzyl benzoate and the benzalkonium chloride, as well as the more known benzene and toluene 30 and its accumulation is indicative of a previous exposure to such toxicants. 31 Patients suffering from MCS and carriers of these genetic anomalies are therefore strongly exposed to the development of phlogistic reactions of various organs and systems, in particular the ocular mucosae, oronasal, and tracheal.…”