Catalytic Efficiencies of Allelic Variants of Human Glutathione S-transferase Pl-1 toward Carcinogenic ¿wft'-Diol Epoxides of Benzo[c]phenanthrene and Benzo^Jchrysene1

Four allelic variants of glutathione (GSH) S-transferase Pl-1 (hGSTPl-1) that differ in their structures at amino acid(s) in position(s) 104 and/or 113 are known to exist in human populations. However, the physiological significance of hGSTPl-1 polymorphism is not fully under stood. In this communication, we report that the I104,AII3 alÃ-eleof hGSTPl-1, which is most frequent in human populations, is also most efficient in the GSH conjugation of carcinogenic onfi'-diol epoxides of benzo[g]chrysene and benzo[c]phenanthrene (a/iri-BGCDE and antiBCPDE, respectively). The catalytic efficiency of hGSTPl-l(I104,A113) isoform toward anri-BGCDE, 0.36 mM~'-s~', was ~1.7-fold higher (P < 0.05) compared with hGSTPl-l(V104,V113). Interestingly, the fre quency of codon 104-valine alÃ-elesis significantly higher in certain cancers compared with codon 104-isoleucine alÃ-eles.Like anri-BGCDE, the cata lytic efficiency of hGSTPl-l(I104,A113) isoform toward an/i-BCPDE was higher by about 1.4to 2.2-fold (P < 0.05) than those of other hGSTPl-1 variants. These observations are interesting because we have shown pre viously (Hu, X. et al., Biochem. Biophys. Res. Commun., 238: 397-402, 1997) that the V104,V113 variant, not the I104,A113 isoform, is most efficient in the GSH conjugation of bay-region anft'-diol epoxide of ben/(>(<(i|i\ n-iic (anft'-BPDE), which, unlike anri-BGCDE or anri-BCPDE, is a planar molecule. In conclusion, our results suggest that hGSTPl-1 poly morphism may be an important factor in differential susceptibility of humans to cancers where polycyclic aromatic hydrocarbons are etiological factors and that I KM.Y113 variant may play a major role in the detoxification of nonplanar, sterically hindered fjord-region diol epoxides (e.g., anri-BGCDE).