Chemistry Reference
In-Depth Information
fractures. Severe cases of bone disease with osteomala-
cia have not been observed in other countries (China)
where exposures started in the 1960s, nutritional fac-
tors are similar to Japan in the 1960s-1990s (but bet-
ter than in Japan during WWII), and where cadmium
intakes have been almost as high as in the endemic area
for Itai-Itai disease in Japan (Nordberg
et al.
, 2002).
The important interaction between iron and cad-
mium in the intestinal mucosa has also been shown
in humans. Iron defi ciency or low iron stores (indi-
cated by low serum ferritin values) increases Cd
uptake in humans (Flanagan
et al.
, 1978). Higher
blood and urine values of Cd were found among
Swedish women with iron defi ciency compared
with women without such defi ciency (Akesson
et al.
,
2002). The probable mechanism of this interaction is
the competition between Fe and Cd for the common
transporter DMT-1 (divalent metal transporter 1) in
the intestinal mucosa. Findings in human entero-
cytes of a close correlation between the expression
of DMT-1 and Cd absorption (Tallkvist
et al.
, 2001)
supports such a mechanism.
In a study in metal-contaminated areas in China,
interactions between cadmium and inorganic arsenic
exposure were demonstrated (Hong
et al.
, 2004,
Nordberg
et al.
, 2005). Although there was a lack of
persons with low arsenic exposure and concomitant
high cadmium exposure, a multiplicative interaction
is still indicated with regard to the prevalence of renal
tubular dysfunction in subgroups exposed to various
combinations of the two metals (Figure 1).
4.3 Interactions Between Lead and Other
Metals
Zinc, a nutritionally essential metal, may affect both
the absorption and toxicity of lead. Lead exposure
in both humans and animals may lead to a decrease
in the activity of the zinc-requiring enzyme ALA-
dehydratase. Simultaneous administration of zinc can
counteract this decrease. Soil and dust measurements
of environmental lead were positively associated with
the blood lead concentrations, regardless of the cor-
responding zinc concentrations in these samples. The
strength of association was 20-46% lower in areas
with high environmental concentrations of zinc. The
fi ndings suggest that zinc infl uences the relationship
between soil and dust lead and the corresponding
blood lead levels (Noonan
et al.
, 2003). Lead has been
shown to interfere with the DNA-binding properties of
Sp1 and Egr-1, both
in vivo
and
in vitro
, and also with
the zinc fi nger protein transcription factor IIIA. Thus,
by targeting zinc fi nger proteins (ZFP), lead may cause
multiple responses through its action on a common
site that is present in enzymes, channels, and recep-
tors (Zawia
et al.
, 2000). Lead may also replace zinc on
heme enzymes (Goyer, 1997).
Experiments in laboratory animals have shown that
nutritional iron defi ciency may increase the gastrointes-
tinal lead absorption, thereby promoting lead toxicity
(Mahaffey 1981), particularly in pregnant women and
young children. Similar fi ndings have been shown in
epidemiological studies among children, suggesting that
Combined effect of Cd and As on kidney in G area
80
100
8
0
80
60
60
60
40
40
40
20
20
20
0
0
5
0
200
2
50
0
0
FIGURE 1
Prevalence (%) of elevated excretion for three biomarker proteins in a metal-contaminated area
of China in relation to combined exposure to Cd and As as indicated by urinary As and Cd excretion. UB2MG,
urinary beta2-microglobulin; UNAG, urinary N-acetylglucosaminidase; UALB, urinary albumin. Reproduced
from Nordberg
et al.
(2005).
