Expression of human glutathione transferases in V79 cells and the effect on DNA adduct-formation of diol epoxides derived from polycyclic aromatic hydrocarbons

V79 cells overexpressing human GST P1-1 (isoleucine or valine at position 105 and alanine at position 114) have been exposed to the (+)- and (-)-anti-enantiomers of trans-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenz (BPDE) and trans-9,10-dihydroxy-11,12-epoxy-9,10,11,12-tetrahydrabenzo[c] (BCDE) and GSH conjugale- and DNA adduct-formation monitored. With both transfectants a several-fold increase in conjugate formation of (+)-anti-BPDE and (-)-anti-BCDE (both with R-absolute configuration at the benzylic oxirane carbon) was observed relative to control cells. As anticipated, increased conjugate formation resulted in decreased formation of DNA adducts, in particular with (+)-anti-BPDE. The results with (-)-anti-BCDE suggest that substrate lipophilicity and thus membrane permeability determine accessibility for GST and thus detoxification efficiency in intact cells. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.