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Detoxication of carcinogenic fjord‐region diol epoxides of polycyclic aromatic hydrocarbons by glutathione transferase P1‐1 variants and glutathione
Author(s) -
Sundberg Kathrin,
Seidel Albrecht,
Mannervik Bengt,
Jernström Bengt
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)01291-5
Subject(s) - gstp1 , carcinogen , glutathione s transferase , glutathione , chemistry , biochemistry , detoxication , enzyme , stereochemistry
Epidemiological studies suggest that individuals differing in the expression of allelic variants of the human glutathione transferase (GST) Pi gene differ in susceptibility to chemical carcinogens such as polycyclic aromatic hydrocarbons (PAH). This study reports the catalytic efficiencies ( 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 GSTP1‐1 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 PAH carcinogenesis due to other reasons than a reduced capacity for detoxifying diol epoxides.