Individual sensitivity to DNA damage induced by styrene in vitro: influence of cytochrome p450, epoxide hydrolase and glutathione S-transferase genotypes.
Styrene is a monomer of great commercial interest; its polymers and copolymers are used in a wide range of applications. In humans, styrene metabolism involves oxidation by cytochrome p450 monooxygenases (CYPs) to styrene-7,8-oxide, an epoxide thought to be responsible for the genotoxic effects of styrene exposure and detoxification by means of epoxide hydrolase (EH) and glutathione S-transferases (GSTs). The objective of this study was to investigate if genetic polymorphisms of metabolic enzymes modulate styrene-induced DNA damage in human leukocytes. CYP2E1, CYP1A1, EH, GSTP1, GSTM1 and GSTT1 polymorphisms were determined in 30 healthy donors and alkaline comet assay was carried out in isolated leukocytes exposed to 5 and 10 mM styrene, using 1% acetone as solvent control. The results obtained suggest that CYP1A1 m1, m2 and m4, CYP2E1 Dra I and GSTP1 (exons 5 and 6) polymorphisms may affect styrene induction of DNA damage in human leukocytes.
Laffon
Blanca
B
Departmento Biología Celular y Molecular, Facultad de Ciencias, Universidade da Coruña, Campus A Zapateira s/n, 15071, A, Coruña, Spain.
Pérez-Cadahía
Beatriz
B
Pásaro
Eduardo
E
Méndez
Josefina
J
D000293:Adolescent; D000328:Adult; D020552:Comet Assay; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D004249:DNA Damage; D004851:Epoxide Hydrolases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D020058:Styrene / Q000633:toxicity*
D007527:Isoenzymes; D020058:Styrene; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases