Inhibition of platelet function by GSTM1-null human peripheral lymphocytesexposed to benzo(a)pyrene-induced challenge

Recent epidemiological studies proposed that the glutathione S-transferase (GST) M1-null genotype may contribute to diseases associated with oxidative stress. The genetic polymorphism exhibited by the GSTM1 may be an importan t factor in risk toward oxidant chemicals. In this study, we investigated t he effect of GSTM1-null genotype in lymphocyte and oxidative stress-depende nt inhibition of platelet aggregation. To determine whether GSTM1 deficienc y is a genetic determinant of cell toxicity toward oxidant chemicals, lymph ocytes were incubated in vitro with low levels of benzo(a)pyrene (BaP), cum ene hydroperoxide (CumOOH), or trans-stilbene oxide that do not decrease ce ll viability, and were assessed for oxidative damage and for the lymphocyte -dependent inhibition of platelet response. Malondialdehyde and carbonyl le vels, and the oxidation of cis-parinaric acid, were used as biomarkers of o xidative stress in lymphocytes. Following stimulation by BaP or CumOOH, whe n peroxidation-dependent changes in these parameters were compared between the GSTM1-null genotype and the positive genotype, no significant differenc es were found between the two genotypes. On the other hand, preincubation o f the lymphocytes with BaP or CumOOH attenuated their inhibitory action on ADP-induced platelet aggregation. However, our results indicate that lympho cytes of individuals with the GSTM1-null genotype have greater inhibitory a ctivity on platelet function after exposure to BaP, but not CumOOH, althoug h they are not more susceptible to in vitro oxidative stress.