Ni(II) Inhibition of MutT dGTPase
Chem. Res. Toxicol., Vol. 9, No. 8, 1996 1381
of nontoxic Ni(II) concentrations on the enzyme. How-
ever, phagocytosis and intracellular dissolution of par-
ticulate nickel compounds, essential for strong nickel
carcinogenesis (34), may provide local Ni(II) concentra-
tions high enough to affect enzyme activity. Also, there
are 7 histidine and 1 cysteine residues in the rat 8-oxo-
dGTPase (35) and 3 histidine and 2 cysteine residues in
the human 8-oxo-dGTPase (36). Cysteine residues are
stronger ligands for Ni(II) in comparison to histidines.
Thus, both the rat and human 8-oxo-dGTPases have
more and stronger putative Ni(II) (and some other
transition metals) binding sites in comparison to MutT,
that might suggest stronger interaction with Ni(II).
Nonetheless, the questions whether or not interaction of
Ni(II) with mammalian 8-oxo-dGTPases does in fact lead
to their inhibition, and whether the magnitude of such
inhibition allows for 8-oxo-dG incorporation into DNA
and results in development of the predicted AfC trans-
version mutations in Ni(II)-treated animals, remain to
be answered.
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Ack n ow led gm en t. The authors would like to thank
Dr. Maurice J . Bessman (The J ohns Hopkins University,
Department of Biology) for the generous gift of the MutT
used in this study. We would also like to thank Dr.
Wojciech Bal for his assistance in searching the IUPAC
Stability Constants Database, Release 2 (IUPAC and
Academic Software, 1995).
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