S. Bernardini et al., Trans-stilbene oxide-induced sister chromatid exchange in cultured human lymphocytes: influence of GSTM1 and GSTT1 genotypes, MUTAGENESIS, 16(3), 2001, pp. 277-281
About 50% and 15% of Caucasians lack the glutathione S-transferase MI (GSTM
1) and TI (GSTT1) genes and the corresponding enzyme activity, respectively
. Both of these polymorphisms have been shown to affect the genotoxicity of
some epoxides in cultured human lymphocytes, Especially GSTT1 appears to b
e important in whole-blood cultures, probably because GSTT1 activity is hig
h in erythrocytes, The in vitro genotoxicity of trans-stilbene oxide (TSO),
a model substrate for GSTM1, has been shown to depend on individual GSTM1
activity. The potential role of GSTM1 genotype, and the possible interferen
ce of GSTT1 genotype, has not previously been examined in this context, We
have studied TSO-induced sister chromatid exchanges (SCEs) in 72 h whole-bl
ood lymphocyte cultures from 24 healthy human donors, representing differen
t combinations of GSTM1 and GSTT1 positive and null genotypes, TSO clearly
increased SCEs in cultures of all donors. The mean number of SCEs per cell
induced by 75 and 150 muM TSO was, respectively, 1.5- and 1.3-times higher
in cultures of GSTM1 null than GSTM1 positive donors, In another experiment
, GSTM1 null individuals showed, in comparison with GSTM1 positive subjects
, a 1.8-fold SCE induction by 50 muM TSO, GSTT1 genotype did not have an un
equivocal effect. Our findings suggest that the lack of the GSTM1 gene, res
ulting in reduced detoxification capacity, increases individual sensitivity
to the genotoxic effects of TSO.