GSTM1, GSTT1, and GSTP1 genotypes and the genotoxicity of hydroquinone in human lymphocytes.
Hydroquinone is a myelotoxin that is found in many foods and is also formed through the metabolism of benzene. Human exposure to benzene is associated with the development of myelodysplastic syndrome and acute myelogenous leukemia. Hydroquinone is genotoxic in several in vitro and in vivo test systems, inducing micronuclei (MN), sister-chromatid exchange (SCE), and chromosomal aberrations. Glutathione S-transferases (GSTs) are a superfamily of polymorphic enzymes involved in the conjugation of reactive chemical intermediates to soluble forms. These enzymes play a key role in the detoxification of endogenous and exogenous compounds, and the polymorphic genes GSTM1, GSTT1, and GSTP1 have been associated with the differential metabolism of several genotoxicants. In the present study, we have evaluated the effect of GSTM1, GSTT1, and GSTP1 polymorphisms on the frequency of MN and SCE induced by hydroquinone in human lymphocytes. Lymphocytes were obtained from 15 healthy non-smoking donors, and their GSTM1, GSTT1, and GSTP1 genotypes determined. Treatment of cultures of the lymphocytes with hydroquinone significantly increased the overall frequencies of MN and SCE (P<0.0001). Individuals with the GSTM1 null genotype had a significantly higher frequency of MN compared with GSTM1-present individuals (P=0.013); in contrast, the GSTM1 genotype had no effect on hydroquinone-induced SCE frequency. The other polymorphisms did not significantly affect the frequencies of MN or SCE. These results suggest that GSTM1 is involved in the metabolic fate of hydroquinone and that polymorphisms in GSTM1 could be related to inter-individual differences in DNA damage arising from the exposure to this compound.
Silva
Maria do Céu
Mdo C
Department of Genetics, Faculty of Medical Sciences, New University of Lisbon, Lisbon, Portugal.
Gaspar
Jorge
J
Duarte Silva
Isabel
I
Faber
Ana
A
Rueff
José
J
D000217:Acyltransferases / Q000235:genetics*; D000328:Adult; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D006873:Hydroquinones / Q000633:toxicity*; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D011110:Polymorphism, Genetic; D011174:Portugal; D012854:Sister Chromatid Exchange / Q000187:drug effects
D000217:Acyltransferases; D005982:Glutathione Transferase; D006873:Hydroquinones; D009153:Mutagens; C491107:GSTT2 protein, human; C413545:glutathione S-transferase T1; C043403:fatty acyl ethyl ester synthase; C031927:hydroquinone