revised final - Agency for Toxic Substances and Disease Registry ...

MERCURY 216
2. HEALTH EFFECTS
1995). This effect was seen at mercury concentrations as low as 1 µM, and the inhibition was greater in
astroglial cells than in the cerebral endothelial cells. At a concentration of 100 µM, however, HgCl2 caused
the stimulation of histamine uptake, which was greater in the cerebral endothelial than in the astroglial cells.
The mechanisms of these dose-dependent effects were considered to be different, with the inhibition of
histamine uptake associated with the loss of the transmembrane Na+ and/or K+ gradient and the stimulation
of histamine uptake by the higher mercury concentration being possibly related to a direct effect on the
histamine transporter.
Sekowski et al. (1997) used an intact human cell multiprotein complex (which they call a DNA
synthesome) to evaluate the effects of mercuric chloride on DNA synthesome-mediated in vitro DNA
replication and DNA synthesis. The authors state that the DNA synthesome has the advantage of providing
the highly ordered environment in which DNA replication occurs while allowing more precise identification
of the mechanism or site of effects than possible from the use of whole cells. The results showed that DNA
replication and DNA polymerase activity, as well as DNA replication fidelity of the human cell
synthesome, were specifically inhibited by mercuric ion at physiologically attainable concentrations. The
results suggest that mercuric ions (at concentrations above 10 µM) actively inhibit the elongation stage of
DNA replication.
It has been shown that Hg ++ promotes dose-dependent toxic effects on heart muscle through actions on the
sarcolemma, the sarcoplasmic reticulum, and contractile proteins (Oliveira et al. 1994). In this study,
inorganic mercury (HgCl 2) was shown to have a dose-dependent effect on rat papillary muscle, with a
concentration of 1 µM causing a small increase in the force of isometric contraction. Concentrations of 2.5,
5, and 10 µM produced a dose-dependent decrease in contractile force. The rate of force development,
however, was effected differently, increasing at 1 and 2.5 µM Hg ++ but decreasing to control levels at 5 and
10 µM concentrations. Oliveira et al. (1994) suggested that this response was due to an observed
progressive reduction in the time to peak tension with increasing mercury concentrations, an effect they
attributed to the binding of mercuric ions to SH groups inducing Ca ++ release from the sarcoplasmic
reticulum, the activity of which itself was depressed by mercury in a dose-dependent fashion. Further,
tetanic tension did not change during treatment with 1 µM Hg ++ but decreased with 5 µM, suggesting a
toxic effect on the contractile proteins only at high Hg ++ concentrations (Oliveira et al. 1994).
The molecular events leading to activation of the autoimmune response in susceptible individuals have yet
to be fully elucidated. However, chemical modification of major histocompatibility complex (MHC) class