Benzo[a]pyrene-induced DNA-protein crosslinks in cultured human lymphocytes and the role of the GSTM1 and GSTT1 genotypes.
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.
Park
Hye-Sook
HS
Department of Preventive Medicine, College of Medicine, Ewha Woman's University, Seoul, Korea.
Ha
Eun-Hee
EH
Lee
Kwan-Hee
KH
Hong
Yun-Chul
YC
D000328:Adult; D001564:Benzo(a)pyrene / Q000633:toxicity*; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000633:toxicity*; D004268:DNA-Binding Proteins; D004305:Dose-Response Relationship, Drug; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008297:Male; D011110:Polymorphism, Genetic
D001564:Benzo(a)pyrene; D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1