Catalytic Efficiency of Glutathione Transferase P1-1 Variants Towards Bay- and Fjord-Region Diol Epoxides of Polycyclic Aromatic Hydrocarbons

Abstract

Polymorphism of the human GSTP gene may be of importance in PAH-induced carcinogenesis. A higher frequency of GSTP*B (encoding for Val at position 105) genotype among individuals with certain tumours has been observed. The altered susceptibility may be associated with a decreased GST-dependent elimination of reactive PAH-intermediates. We have determined the catalytic efficiency of two naturally occurring GSTP1-1 allelic variants with Ile or Val at position 105 towards bay- and fjord-region diol epoxides of chryscne (CDE) and dibenzo[a, l]pyrene (DBPDE), respectively. With both variants, the bay-region diol epoxides were more efficiently conjugated than the fjord-region analogues. GSTP1-1/Val was about 3-fold more active with (+)-anti-CDE relative to GSTP1-1/Ile. With (+)-syn-CDE, equal activity was observed. GSTP1-1/Val was about 2-fold more efficient than the Ile-variant with (-)-anti-DBPDE. No difference in activity was observed with (+)-syn-DBPDE.