Carcinogenesis, Vol 19, 1685-1689, Copyright © 1998 by Oxford University Press
X Hu, A Pal, J Krzeminski, S Amin, YC Awasthi, P Zimniak and SV Singh
The specificities of human glutathione (GSH) S-transferase (GST) isozymes
of class alpha (hGSTA1-1), mu (hGSTM1-1) and pi (hGSTP1-1), including the
three allelic forms of hGSTP1-1 [hGSTP1-1(I104,A113), hGSTP1-1(V104,A113)
and hGSTP1-1(V104,V113)], in catalyzing the GSH conjugation of anti-diol
epoxide stereoisomers of 5-methylchrysene (anti-5-MeCDE) have been
examined. The specific activities of human GSTs were significantly higher
toward (+)-anti-5-MeCDE than toward the (-)-enantiomer of anti-5-MeCDE. All
three variants of hGSTP1-1 were significantly more efficient than either
hGSTA1-1 or hGSTM1-1 in GSH conjugation of (+)-anti-5-MeCDE. The catalytic
efficiencies of hGSTP1-1 variants toward (+)-anti-5-MeCDE were in the order
hGSTP1-1(I104,A113) > hGSTP1-1(V104,V113) > hGSTP1-1(V104,A113). The
present study suggests that the I104,A113 allele, which is most frequent in
human populations, may play a major role in the detoxification of
(+)-anti-5-MeCDE. This may point to specificity, because previous studies
from our laboratory have shown that the hGSTP1-1(V104,V113) isoform is
significantly more efficient than the other two variants of hGSTP1-1 in
catalyzing GSH conjugation of
(+)-anti-7R,8S-dihydroxy-9S,10R-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene
[(+)-anti-BPDE], the ultimate carcinogen of benzo[a]pyrene. Even though the
mechanism of the differences in the activities of hGSTP1-1 variants toward
anti-5-MeCDE versus anti-BPDE remains to be elucidated, it seems that the
molecular configuration of the diol epoxide is an important determinant of
the activity of hGSTP1- 1 isoforms toward polycyclic aromatic hydrocarbon
diol epoxides.
ARTICLES
Specificities of human glutathione S-transferase isozymes toward anti- diol epoxides of methylchrysenes
Cancer Research Laboratory, Mercy Cancer Institute, The Mercy Hospital of Pittsburgh, PA 15219, USA.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. Johnson, P. J. Orchard, K. S. Baker, R. Brundage, Q. Cao, X. Wang, E. Langer, S. F.-E. Maasah, J. A. Ross, R. Remmel, et al. Glutathione S-Transferase A1 Genetic Variants Reduce Busulfan Clearance in Children Undergoing Hematopoietic Cell Transplantation J. Clin. Pharmacol., September 1, 2008; 48(9): 1052 - 1062. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Fowke, X.-O. Shu, Q. Dai, A. Shintani, C. C. Conaway, F.-L. Chung, Q. Cai, Y.-T. Gao, and W. Zheng Urinary Isothiocyanate Excretion, Brassica Consumption, and Gene Polymorphisms among Women Living in Shanghai, China Cancer Epidemiol. Biomarkers Prev., December 1, 2003; 12(12): 1536 - 1539. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kuljukka-Rabb, K. Peltonen, S. Isotalo, S. Mikkonen, L. Rantanen, and K. Savela Time- and dose-dependent DNA binding of PAHs derived from diesel particle extracts, benzo[a]pyrene and 5-methylchrysene in a human mammary carcinoma cell line (MCF-7) Mutagenesis, July 1, 2001; 16(4): 353 - 358. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Wang, T. K. Bammler, Y. Guo, E. J. Kelly, and D. L. Eaton Mu-Class GSTs Are Responsible for Aflatoxin B1-8,9-Epoxide-Conjugating Activity in the Nonhuman Primate Macaca fascicularis Liver Toxicol. Sci., July 1, 2000; 56(1): 26 - 36. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. F. Coles, K. E. Anderson, D. R. Doerge, M. I. Churchwell, N. P. Lang, and F. F. Kadlubar Quantitative Analysis of Interindividual Variation of Glutathione S-Transferase Expression in Human Pancreas and the Ambiguity of Correlating Genotype with Phenotype Cancer Res., February 1, 2000; 60(3): 573 - 579. [Abstract] [Full Text]
|
|