Glutathione Conjugation and DANN Adduct Formation of Diol Epoxides in V79 Cells Expressing Human Glutathione Transferase P1-1

V79 cells and cells over-expressing glutathione transferase (GST) P1-1 have been incubated with the (+)- and (-)-anti-enantiomers of trans-7,8-dihydroxy-9,10-epoxy- 7,8,9,10-tetrahydrobenzo [a] pyrene (BPDE) and trans-9,10-dihydroxy-11,12-epoxy-9,10,11,12-tetrahydrobenzo [c] chrysene (BCDE) and the formation of glutathione (GSH) conjugates and DNA adducts monitored. With (+)-anti-BPDE and (-)-anti-BCDE, the results demonstrate a several fold increase in conjugate formation concomitant with reduced levels of DNA adducts in GST expressing cells relative to control cells. Thus, the effects were restricted to the enantiomers with R-absolute configuration at the benzylic oxirane carbon. The rate of conjugate formation of BCDE relative to BPDE is significantly lower indicating reduced accessibility of the more lipophilic BCDE for GSTP1-1.