Mercury - Toxicology of Metals - page 669

according to all available evidence, be attributed to
the divalent mercury ion formed through oxidation in
the tissue. Just as some Hg-thiol-complexes can mimic
endogenous molecules at the site of proteins present
in the plasma membrane, these complexes may also
mimic molecules at the binding site(s) of intracellu-
lar proteins and enzymes. Because Cys- S -Hg- S -Cys
mimics cystine at the site of an amino-acid transporter
on the plasma membrane (Bridges et al ., 2004), it is
not surprising to fi nd that this conjugate also acts as
a mimic of this amino acid at binding sites of intra-
cellular molecules that use cystine as a substrate.
An example of this mimicry has been demonstrated
by the preliminary fi ndings of Cooper and colleagues
(unpublished data), which indicate that Cys- S -Hg- S -
Cys acts as a mimic of cystine at the binding site of the
intracellular enzyme,

On the other hand, mercury has occurred in the envi-
ronment throughout evolution, and organisms have
acquired the ability to manage limited quantities of
this metal. Special molecules containing SH-groups or
SeH-groups and with an ability to bind strongly to Hg +2
have been identifi ed (Nordberg et al , 1974; Yoneda and
Suzuki, 1997). Glutathione and metallothionein are mol-
ecules that can neutralize the mercury ion and prevent it
from disturbing the cell's dynamic biochemical systems.
Bound to these molecules, mercury can be transported,
stored, and eliminated from the body. It has also been
shown experimentally that the sensitivity of different
cell types to the mercury's cytotoxic effects is related to
their ability to synthesize glutathione or metallothionein
(Bohets et al ., 1995; Foulkes, 1993; Kim et al ., 1995b). Bind-
ing to metallothioneins explains, for example, why such
high mercury concentrations can be encountered in the
kidneys without production of metabolic disturbances.
Because the metabolism and toxic properties of metal-
lic mercury, especially in vapor form, and mercuric mer-
cury differ considerably, they are treated separately below.
It should also be noted that many of the studies reported
in the older literature should be considered in light of
limitations in mercury analyses and quality control.

-cystathionase. This enzyme is
activated normally by the binding of cystine or cys-
tathionine. Because the binding of Cys- S -Hg- S -Cys
was shown to inactivate the enzyme, rather than acti-
vate it, it can be concluded that this conjugate behaves
as a structural, but not a functional, mimic of cystine
and cystathionine. These fi ndings suggest that the
ability of molecular species of metals to mimic endog-
enous molecules may have serious, deleterious effects
on intracellular processes.
More specifi cally, it has long been known that Hg +2
is cytotoxic. SH-groups constitute an important com-
ponent in proteins. Mercury binding to these groups
can produce a change in the proteins' tertiary and qua-
ternary structure and alter binding conditions in pros-
thetic groups in enzymes (Freitas et al ., 1996; Palkiewicz
et al ., 1994; Pendergrass & Haley, 1997; Rajanna et al .,
1995) and block or modify receptor binding (Albrecht
& Matyja, 1996; Castoldi et al ., 1996; Kim and Choi,
1995) and K − or Ca − ion fl ows in the cell membrane's
pores and ionic channels (Aschner et al ., 1996; Bussel-
berg, 1995; Dyatlov et al ., 1996; Fejtl et al ., 1994; Leon-
hardt et al ., 1996; Rossi et al ., 1993; Szucs et al ., 1997;
Yallapragada et al ., 1996). This can affect cell membrane
potentials and intracellular and intercellular signals.
The release of transmitter substances in nerve cells can
be inhibited or accelerated, as is cytokine production in
the cells of the immune system and hormone produc-
tion in endocrine glands. It has been possible to observe
these effects in in vitro experiments with cell cultures of
different types of cells or with the help of intracellu-
lar electrodes in single cells and with a 0.1-1

γ

6.1 Elemental Mercury
6.1.1 Metabolism

6.1.1.1 Absorption Inhalation
Mercury vapor is effi ciently absorbed from the alveo-
lar air because of the rapid diffusion of mercury vapor
through the alveolar membrane (Berlin et al ., 1969b) and
because of the capacity of red cells to bind and to oxidize
mercury to mercuric mercury (Clarkson et al ., 1961). The
oxidation of mercury and the red cells occurs, at least
partly, under the infl uence of catalase (Halbach and Clark-
son, 1978; Magos et al ., 1978). This oxidation can, however,
be inhibited by alcohol and aminotriazole (Magos et al .,
1974; Nielsen-Kudsk, 1965), whereby the absorption and
retention by inhalation are reduced. Considering the
effect of deadspace, the absorption of mercury vapor at
moderate ventilation rates will be approximately 80% at
concentration levels encountered in the working environ-
ment (Nielsen-Kudsk, 1965). Similar absorption rates were
obtained after exposure of volunteers to small amounts of
radioactive mercury vapor (Hursh et al ., 1976).

mol/L
mercury concentration in the medium (Berlin, 1999).
In cultures of fetal brain tissue, growth inhibition and
changing concentration of growth factors have been
reported at mercury concentration approximately 0.01
µ

µ

6.1.1.2 Ingestion
Liquid metallic mercury is poorly absorbed from
the gastrointestinal tract. Mercury vapor is slowly
released from the surface of metallic mercury at a rate
that is related to the surface area present. The tendency
of metallic mercury to cover itself with mercury sulfi de

mol/L (Abdulla et al ., 1995; Monnet-Tschudi et al .,
1996; 1998; Soderstrom et al ., 1995).