Journal of Clinical Toxicology
Open Access

Benzene and styrene metabolism: Influence of genetic polymorphisms of detoxification enzymes on the urinary excretion of occupational exposure biomarkers

7^th Euro-Global Summit on Toxicology & Applied Pharmacology

October 24-26, 2016 Rome, Italy

Damiano Carbonari, Rossana Claudia Bonanni, Marzia Fioretti, Maria Pia Gatto, Monica Gherardi, Antonella Mansi, Maddalena Papacchini, Anna Rita Proietto, Renata Sisto and Giovanna Tranfo

Istituto Nazionale Assicurazione Infortuni sul Lavoro, Catone, Italy

Posters & Accepted Abstracts: J Clin Toxicol

Abstract :

Susceptibility to chemicals may derive from genetic or acquired characteristics. Toxic chemicals once adsorbed are biotransformed to compounds that may be more toxic than the original or converted into non-toxic metabolites that are excreted through the urine (detoxification). Genetic polymorphisms of xenobiotic metabolizing enzymes may lead to relevant shifts in the balance of bioactivation and detoxification pathways. The aim of this work was to evaluate the influence of the polymorphisms of CYP2E1, GSTs and mEH enzymes in the detoxification pathways of 2 occupational toxicants, benzene and styrene; determining the excretion variability of the urinary metabolites used as exposure biomarkers: This variability can significantly affect the biological monitoring studies for exposure assessment. In benzene exposed workers a strong influence of GSTT1 polymorphism on the excretion of S-phenyl mercapturic acid was found, reducing the conjugation rate of benzene epoxide with GSH in null subjects of about 50% with respect to the GSTT1 positive genotype for the same benzene exposure. To a lesser extent a similar effect is seen for GSTA1 mutant and GSTM1 null genotypes. In styrene exposed workers the CYP2E1*5B and CYP2E1*6 heterozygote alleles reduce the excretion of mandelic and phenyl glyoxylic acids to about 20% with respect to the wild type genotype, in the 7.5% and 13.8% of the population respectively, and the slow EPHX1 allele (codon 113) of 35% in the 17.8% of the population. A significant correlation also exists between the predicted activity profile of mEH and the excretion levels of styrene metabolites.

Biography :

Email: d.carbonari@inail.it