Overexpression of stably transfected human glutathione S-transferase P1-1 protects against DNA damage by benzo[a]pyrene diol-epoxide in human T47D cells

Fields, W.R.; Morrow, C.S.; Doss, A.J.; Sundberg, K.; Jernström, B.; Townsend, A.J.

Molecular Pharmacology 54(2): 298-304

1998


ISSN/ISBN: 0026-895X
PMID: 9687571
DOI: 10.1124/mol.54.2.298
Accession: 046897196

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Abstract
The (+)-anti enantiomer of benzoBPDE adduct formation and did not affect sensitivity to BPDE-induced cytotoxicity. Protection against BPDE-induced cytotoxicity was observed only in the T47Dpi cell line, which had an IC50 value 5.8-fold greater than that of the T47Dneo control cell line. Measurement of glutathione conjugates of BPDE indicated that the total conjugation was 5-fold higher in the GSTpi-transfected T47D line, most of which was exported into the culture medium over the 20-min exposure period. These results indicate that hGSTP1-1 protects effectively against DNA and RNA modification by BPDE, but moderate to high level expression may be required for strong protection against BPDE-induced genotoxicity and cytotoxicity.