Chemistry Reference
In-Depth Information
Some aspects illustrating the importance of
biotransformation (formation or breakdown of metal-
carbon bonds [e.g., breakdown of organomercurials
to inorganic mercury] or change of oxidation state of
a metal in the biological system) are given in Chap-
ter 33. The importance of the oxidation of mercury
vapor to mercuric ion for the toxic effects on the CNS
is described in Chapter 33 in some detail. Exposure
to mercury vapor also exemplifi es the importance of
a rapid vascular perfusion for distribution. The rapid
perfusion of the brain makes it possible that physi-
cally dissolved mercury vapor is transported from
the lung to the brain before Hg
0
is oxidized to Hg
++
in the blood. The vapor can penetrate the blood-brain
barrier and will thereafter be oxidized to Hg
++
, which
will be “trapped” in the cells of the CNS and exert its
toxic effect. Hexavalent chromium is an example of
transport into the cells followed by metabolic reduc-
tion to trivalent chromium that is assumed to induce
mutations and ultimately carcinogenesis by a direct
reaction with DNA (Figure 8).
The methylation and/or demethylation of metallic
compounds is of great importance for toxicity. Whereas
methylation processes are of importance as a detoxi-
fying process for arsenic in most animals and man
(Buchet
et al.
, 1981; Vahter and Norin, 1980), demeth-
ylation serves as an important step in the detoxifi ca-
tion and elimination of mercury from animals and man
after exposure to methylmercury, as will be discussed
in more detail in the next section. The breakage of one
carbon-metal bond in tetraethyl tin, on the other hand,
yields a highly toxic metabolite (triethyl tin) believed
to be responsible for the toxic effects (Cremer, 1959).
MeHg-L-Cys
40
30
20
MeHg-D-Cys
10
0
0
500
1000
1500
2000
MeHg-cysteine (
µ
m)
FIGURE 7
The uptake from plasma to brain in rats of the L and
D optical isomers of the mercury-cysteine complex. (From Kerper
et al.,
1992).
Studies on methylmercury secretion into bile indicate
that methylmercury is extruded from cells as a com-
plex with glutathione on the reduced glutathione car-
rier (Ballatori and Clarkson, 1982; 1983; Refsvik and
Norseth, 1975). Thus, transport across the endothelial
cell of the blood-brain barrier probably involves a step-
wise process: transport into the cell on the large neu-
tral amino acid carrier, the exchange of methylmercury
from a cysteine thiol to one on glutathione because the
latter is present inside the cell at much higher concen-
trations than cysteine, and fi nally transport out of the
cell on the glutathione carrier.
Extracellular
Cell membrane
Intracellular
Cr
Y
CrO
=
CrO
=
CrO
=
SO
4
CARRIER
GSH
GS
−
DNA
CANCER
FIGURE 8
Diagrammatic representation of the entry of the chromate oxyanion into the cell of
the sulfate carrier and its subsequent reduction to trivalent chromium. The latter forms complexes
with DNA to produce mutations that may ultimately lead to cancer.
