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B. LAFFON LAGE Y COLS. AN. R. ACAD. NAC. FARM.

y GSTT1 no se obtuvieron resultados claros, incluso tras agrupar a los individuos
con la misma actividad epóxido hidrolasa esperada, problablemente debido a que
la conjugación con glutation juega un papel minoritario en el metabolismo del
estireno.

Palabras clave: Estireno.—Test de micronúcleos.—Ensayo del cometa.—Poli-
morfismos genéticos.—Glutation S-transferasa.—Epóxido hidrolasa.

SUMMARY

Influences of certain polymorphisms of metabolic enzymes
in the genotoxicity of the styrene

Styrene is an organic chemical of great commercial interest widely used in the
manufacture of many industrial products. Exposure to styrene has been associated
with genotoxic effects, mainly after metabolic activation to styrene-7,8-oxide (SO).
SO is detoxified by epoxide hydrolase or, to a minor extent, by glutathione S-
transferases. In the present study we have evaluated the influence of the following
factors in the genotoxicity of SO in human leukocytes: physiologic and lifestyle
factors, and genetic polymorphisms in the mentioned metabolic enzymes (EPHX1
exons 3 and 4, GSTP1 exons 5 and 6, and GSTM1 and GSTT1 deletion polymor-
phisms). The experimental design consisted in exposure of peripheral leukocytes
from 30 healthy donors to two SO doses, or to a solvent control, and evaluation of
genotoxicity by means of micronucleus (MN) test and comet assay. Results obtai-
ned show that MN frequency and DNA damage induced by SO are affected by age;
however influence of tobacco consum has not been detected, and sex effect is few
clear. An increase in induced comet tail length with decreasing epoxide hydrolase
activity in SO-exposed cells, and an increase in MN frequency in low activity
donors was observed. This findings are consistent with the detoxifying activity of
this enzyme. In addition, increases in MN frequencies for GSTP1 *A/*B and *A/*C
genotypes with regard to the wild-type homozygous *A/*A genotype were detected.
This may be due to a low detoxifying activity as a consequence of altered SO
affinity of the variant protein. No clear results were obtained for GSTM1 or GSTT1
genotypes, even when performing the analysis after grouping individuals with the
same expected epoxide hydrolase activity, probably due to the minor role that
glutathione conjugation plays in styrene metabolism.

Keywords: Styrene.—Micronucleus test.—Comet assay.— Genetic polymorphis-
ms.—Glutathione S-transferase.—Epoxide hydrolase.

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