Expression of human glutathione transferases in V79 cells and the effect on DNA adduct-formation of diol epoxides derived from polycyclic aromatic hydrocarbons
K. Sundberg et al., Expression of human glutathione transferases in V79 cells and the effect on DNA adduct-formation of diol epoxides derived from polycyclic aromatic hydrocarbons, CHEM-BIO IN, 133(1-3), 2001, pp. 91-94
V79 cells overexpressing human GST P1-1 (isoleucine or valine at position 1
05 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 transfect
ants a several-fold increase in conjugate formation of (+)-anti-BPDE and (-
)-anti-BCDE (both with R-absolute configuration at the benzylic oxirane car
bon) was observed relative to control cells. As anticipated, increased conj
ugate formation resulted in decreased formation of DNA adducts, in particul
ar with (+)-anti-BPDE. The results with (-)-anti-BCDE suggest that substrat
e lipophilicity and thus membrane permeability determine accessibility for
GST and thus detoxification efficiency in intact cells. (C) 2001 Elsevier S
cience Ireland Ltd. All rights reserved.