Exposure to low environmental levels of benzene: evaluation of micronucleus frequencies and S-phenylmercapturic acid excretion in relation to polymorphisms in genes encoding metabolic enzymes.
An integrated approach based on environmental and biological monitoring, including the analysis of biomarkers of exposure [excretion of S-phenylmercapturic acid (S-PMA)], early biological effects [micronucleus (MN) frequency] and susceptibility (genetic polymorphisms), was applied to characterize benzene exposure in a group of 70 traffic policemen and 40 employees of the city of Bologna, Italy. Median personal benzene exposure was 6.55-fold higher for traffic policemen than for controls (P<0.0001). This higher exposure was confirmed by a significant, 2.53-fold higher S-PMA excretion in traffic policemen compared with that observed for indoor workers (P<0.0001). Median MN frequency was also significantly higher in policemen compared with indoor workers (P=0.001), emphasizing the genotoxic effect potentially associated with benzene exposure. With regard to biomarkers of susceptibility, the analysis revealed that high epoxide hydrolase (mEH) (predicted) enzyme activity was significantly correlated with a lower median MN frequency (P=0.003). A gene-gender interaction was observed for the glutathione-S-transferase M1 (GSTM1) genotype. The GSTM1-null genotype was associated with a significantly higher median MN frequency in men, not in women. Statistical analysis did not reveal any association between the presence of the protective allele, pushing the pathway towards benzene detoxification, and MN frequency or S-PMA excretion. Even though there are some limitations in the study, our results indicate that policemen are exposed to higher levels of benzene than individuals spending most of the time indoors. This higher exposure may contribute to DNA damage, suggesting an increase health risk from traffic benzene emission. Finally, a more comprehensive study is warranted in order to better elucidate the involvement of EPHX1 genotypes combination in benzene genotoxicity.
Department of Pharmacology, University of Bologna, Via Irnerio 48, Bologna 40126, Italy. s.angelini@unibo.it
Sabrina
S
Angelini
Rajiv
R
Kumar
Justo Lorenzo
JL
Bermejo
Francesca
F
Maffei
Anna
A
Barbieri
Francesca
F
Graziosi
Fabio
F
Carbone
Giorgio
G
Cantelli-Forti
Francesco Saverio
FS
Violante
Kari
K
Hemminki
Patrizia
P
Hrelia
D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000652:urine; D000328:Adult; D001554:Benzene / Q000032:analysis* / Q000506:poisoning; D004785:Environmental Pollutants / Q000032:analysis* / Q000506:poisoning; D004851:Epoxide Hydrolases / Q000235:genetics / Q000378:metabolism; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007558:Italy; D016014:Linear Models; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced; D015162:Micronucleus Tests / Q000706:statistics & numerical data; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects / Q000032:analysis*; D016495:Police; D011110:Polymorphism, Genetic; D018570:Risk Assessment / Q000379:methods / Q000706:statistics & numerical data; D012307:Risk Factors; D012737:Sex Factors; D055815:Young Adult
D000111:Acetylcysteine; D001554:Benzene; D004785:Environmental Pollutants; D004851:Epoxide Hydrolases; D005982:Glutathione Transferase; C053003:S-phenyl-N-acetylcysteine