Chemistry Reference
In-Depth Information
(D'Agostini
et al.
, 2000). NAC prevented the adverse
effects of AsA on spontaneous mutagenicity. At the
same time, this thiol and AsA showed additive effects,
inhibiting the mutagenicity of Cr (VI) and the lung tum-
origenicity of urethane in mice (D'Agostini
et al.
, 2000).
Experiments on Chinese hamster ovary cells using
a host cell reactivation assay showed that the repair of
BPDE-DNA adduct in a luciferase reporter gene was
greatly inhibited after Cr(VI) exposure in NER-profi -
cient cells but not in NER-defi cient cells. Accordingly,
Cr(VI) exposure can greatly enhance the mutagenic-
ity and cytotoxicity of PAHs by inhibiting the cellular
NER pathway, and this may constitute an important
mechanism for Cr(VI)-induced human carcinogenesis
(Hu
et al.
, 2004).
might be responsible for the observed carcinogenicity
(Park
et al.
, 2002).
An elevated dietary iron intake enhances the inci-
dence of carcinogen-induced mammary tumors in rats
and estrogen-induced kidney tumors in Syrian ham-
sters. Estrogen administration increases iron accumu-
lation in hamsters and facilitates iron uptake by cells
in culture. In humans, increased body stores of iron
have been shown to increase the risk of several estro-
gen-induced cancers (e.g., breast cancer; Liehr and
Jones [2001]).
In cell experiments, addition of catalase, which can
increase Fe
2+
concentrations, further increased the
plasmid-induced DNA damage; on the other hand,
diethylenetriaminepentaacetic acid (an iron chela-
tor) signifi cantly inhibited DNA damage. Thus, iron-
dependent DNA damage has been suggested as one
mechanism of action of human arsenic carcinogenesis
(Ahmad
et al.
, 2002). The iron chelator phenanthroline
suppressed the sodium chloride-enhanced gastric car-
cinogenesis induced by N-methyl-
N
'-nitro-
N
-nitro-
soguanidine in experiments on Wistar rats (Tatsuta
et al.
, 2003). Intraperitoneal administration of fer-
ric iron-ATP (FeATP) has been studied in an animal
model. The morbidity and mortality rate were higher
with FeATP, indicating two different interactions
(intensity and duration) with the cell plasma mem-
brane (Anghileri
et al.
, 2002).
Ex vivo
and
in vitro
protective effects of kolaviron
against oxygen-derived radical-induced DNA damage
and oxidative stress have been found in human lym-
phocytes and rat liver cells. One mechanism behind
the protective effects versus oxidative damage to
molecular targets may be by means of scavenging of
free radicals and iron binding (Farombi
et al.
, 2004).
5.3 Iron
Iron can induce the production of free radicals,
which may cause DNA double-strand breaks and
oncogene activation. Iron can also maintain the
growth of malignant cells, as well as the growth of
pathogens. Breast cancer cells have been shown to
display 5-15 times more transferrin receptors than
normal breast tissue cells. On the other hand, iron che-
lators can counteract cell damage (Reizenstein, 1991).
Animal experiments have shown that magnesium
antagonizes nickel-induced carcinogenesis in the rat
kidney, whereas iron tends to enhance it (Kasprzak
et al.
, 1994). Experiments on hamsters have shown
that estrogen treatment increased the non-heme iron
in liver of both high and low iron treatment groups
and in kidney of the hamsters on the low-iron diet.
Thus, the dietary iron enrichment may enhance the
incidence and severity of estrogen-induced tumor
induction (Wyllie and Liehr, 1998).
Iron may act as a promoter of dimethylnitrosamine-
initiated hepatocytes in rats. Fibrogenesis was not an
absolute requirement for this promotion. The authors
suggest that iron may also act as a promoter of already
initiated hepatocytes in the development of liver cancer
in humans (Carthew
et al.
, 1997).
In experimental studies, 2-butoxyethanol increased
liver tumors in B6C3F1mice after chronic exposure.
Continued treatment with 2-butoxyethanol resulted in
hemosiderin deposition in the liver, indicating that the
liver tumors were mediated by oxidative iron catalyzed
stress and Kupffer cell activation (Park
et al.
, 2002).
Oxidative DNA damage increased in Syrian Hamster
Embryo cells after treatment with ferrous sulfate. On
the other hand, the DNA lesions decreased by cotreat-
ment of ferrous sulfate with antioxidants. The authors
suggested that iron, produced indirectly through
hemolysis and not 2-butoxyethanol or its metabolites,
5.4 Lead
Lead chromate can induce chromosomal damage.
In cell experiments, high doses of lead glutamate were
weakly clastogenic. It induced a different spectrum of
chromosomal aberrations compared with lead chro-
mate. Pretreatment of cells with vitamin E reduced the
lead chromate-induced clastogenesis by 54-93% (Wise
et al.
, 1994).
Lead, as well as cadmium, may act as a tumor pro-
moter in diploid human fi broblasts. In the experiments,
ROS had a greater impact on cadmium than on lead-
induced cytotoxicity and anchorage independence
(Hwua and Yang, 1998).
It has been suggested that lead on a cellular and
molecular level may permit or enhance carcinogenic
events involved in DNA damage, DNA repair, and
regulation of tumor suppressor and promoter genes
