DETOXICATION OF CARCINOGENIC FJORD-REGION DIOL EPOXIDES OF POLYCYCLICAROMATIC-HYDROCARBONS BY GLUTATHIONE TRANSFERASE P1-1 VARIANTS AND GLUTATHIONE

Epidemiological studies suggest that individuals differing in the expr ession of allelic variants of the human glutathione transferase (GST) Pi gene differ in susceptibility to chemical carcinogens such as polyc yclic aromatic hydrocarbons (PAH). This study reports the catalytic ef ficiencies (k(cat)/K-m) of two naturally occurring variants, GSTP1-1/I -105 and GSTP1-1/V-105, towards a series of fjord-region diol epoxides representing potent biologically active PAH metabolites, and two GSTP 1-1 mutants with Ala(105) and Trp(105) in the active site, The results indicate that individuals who are homozygous for the allele encoding GSTP1-1/V-105 might be more susceptible to PAI-I carcinogenesis due to other reasons than a reduced capacity for detoxifying diol epoxides. (C) 1998 Federation of European Biochemical Societies.