4.4
Genetic and related effects
4.4.1
Humans
Lener et al. (1998) studied children exposed to vanadium in air in an area close to a
plant processing vanadium-rich slag (see Section 4.2.3). Group A comprised 15 children
from the area potentially most affected by vanadium emissions; Group B, 28 children from
an area of medium exposure; and Group C, 32 children was the control group. No signi-
ficant induction of chromosomal aberrations was found in the lymphocytes of exposed
children (1.2
± 1.2 in Group A; 1.3 ± 1.1 in Group B) compared with the control group
(0.95
± 0.97). Sister chromatid exchange was analysed in exposed children (4.6 ± 1.0 in
Group A; 4.6
± 0.87 in Group B) but no data were available from controls. However, the
authors concluded that these results revealed no genotoxic effects of vanadium exposure.
Only one in-vivo study of the genotoxic action of vanadium pentoxide in adult
humans has been reported. Ivancsigts et al. (2002) studied the effect of occupational expo-
sure to vanadium pentoxide by measuring DNA strand breaks using the single-cell gel
electrophoresis assay ‘Comet Assay’, formation of 8-hydroxy-2´-deoxyguanosine, and the
frequency of sister chromatid exchange in whole blood or lymphocytes of 49 male
workers in a vanadium-processing factory. Although there was significant vanadium
uptake (mean vanadium concentration in serum, 5.38
µg/mL), no increase in cytogenetic
end-points nor in oxidative DNA damage was observed in the cells from these workers.
4.4.2
Experimental systems
(a)
Biochemical assays
Effects of vanadium compounds on DNA-metabolizing enzymes have been reported
by Sabbioni et al. (1983). Vanadate(V) ions (10
–7
–10
–3
M) inhibited calf thymus terminal
deoxynucleotidyl transferase (with an apparent Ki of 2.5
µM) and the catalytic activity of
mammalian DNA polymerase
α (at I
50
of 60
µM), while bacterial DNA polymerase-I was
inhibited when the concentration was increased to about 0.5 mM.
(b)
Mutagenicity (see Table 7)
(i)
In-vitro studies
The mutagenicity of vanadium compounds has been reviewed (Graedel et al., 1986;
Léonard & Gerber, 1994; Altamirano-Lozano et al., 1998b; Léonard & Gerber, 1998;
National Toxicology Program, 2002).
The majority of the results of mutagenic activity of vanadium have been shown in
Escherichia coli and Salmonella typhimurium (Hansen & Stern, 1984; Graedel et al., 1986;
Leonard & Gerber, 1994); there is one study only with exogenous metabolic activation
(National Toxicology Program, 2002).
Early studies demonstrated that vanadium pentoxide was more genotoxic in recombi-
nation-repair-deficient (rec
–
) strains of Bacillus subtilis than in the wild-type rec
+
IARC MONOGRAPHS VOLUME 86
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V
ANADIUM PENT
OXIDE
271
Table 7. Genetic and related effects of vanadium pentoxide
Result
a
Test system
Without
exogenous
metabolic
system
With
exogenous
metabolic
system
Dose
b
(LED/HID)
Reference
Escherichia coli,
spot test B/r WP2try
–
, WP2hcr
–
try
–
–
NT
0.5 M
Kanematsu
et al. (1980)
Escherichia coli, WP
2
, WP
2
uvrA, CM
891
, reversion assay
+
NT
1200
µg/plate
Si et al. (1982)
c
Escherichia coli, ND160 and MR102, frameshift mutation
–
1200
µg/plate
Si et al. (1988)
c
Bacillus subtilis,
M45 recombination-repair-deficient (rec
–
)
+
NT
0.5 M
Kanematsu & Kada
(1978); Kada et al. (1980);
Kanematsu et al. (1980)
Bacillus subtilis H17 (rec
+
) and M45 (rec
-
) recombination-repair-
deficient
+
NT
100 000
Sun (1996)
Salmonella typhimurium, TA100, TA1535, TA1537, TA1538, (his
–
)
–
NT
0.5 M
Kanematsu et al. (1980)
Salmonella typhimurium, TA100, TA98, TA102, TA1535
reverse
mutation
–
–
333
µg/plate
National Toxicology
Program (2002)
Salmonella typhimurium, TA97, TA98, TA100, TA102 reverse
mutation
–
NT
200
µg/plate
Zen et al. (1988)
c
Gene mutation, 6-thioguanine resistant mutation, Chinese hamster lung
fibroblast cell line (V79) in vitro
–
4
Zhong
et al. (1994)
Sister chromatid exchanges, Chinese hamster lung fibroblast cell line
(V79)
in vitro
–
4
Zhong et al. (1994)
Micronucleus formation in binucleated cells, cytochalasin-B assay,
Chinese hamster lung fibroblast cell line (V79) in vitro
+
NT
1
Zhong et al. (1994)
Numerical chromosomal aberrations, endoreduplication, Chinese
hamster lung fibroblast cell line (V79) in vitro
+
1
Zhong
et al. (1994)
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