Benzo[a]pyrene-induced DNA-protein crosslinks in cultured human lymphocytes and the role of the GSTM1 and GSTT1 genotypes.

Abstract

We investigated the influence of glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1) polymorphisms upon DNA-protein crosslinks (DPC) induced by benzo[a]pyrene (B[a]P) in cultured human lymphocytes. Lymphocyte samples were collected from 30 healthy nonsmoking hospital administrative workers. DPC was detected with KCl-SDS assay and the distributions of GSTM1 and GSTT1 were determined by polymerase chain reaction. B[a]P was found to induce a significant dose-responsive increase in cytotoxicity and DPC regardless of the genotypes (p<0.05). We did not find statistically significant genetic modification effect of GSTM1 and GSTT1 polymorphisms in the cytotoxicity and DPC formation (p>0.05). In terms of the genes examined, the level of cytotoxicity and DPC formation were found to be highest in the GSTM1-null and GSTT1-null cells. In conclusion, B[a]P induced a significant increase in the cytotoxicity and the level of DPC formation in cultured human lymphocytes. Our findings suggest that DPC could be used as a biomarker of B[a]P exposure.