ARTICLE IN PRESS
Environmental Research 101 (2006) 349–355
www.elsevier.com/locate/envres
Arsenic speciation transported through the placenta from mother mice
to their newborn pups
Yaping Jina, Shuhua Xib, Xin Lia, Chunwei Lua, Gexin Lia, Yuanyuan Xua, Chunqing Qua,
Yuhong Niua, Guifan Suna,
a
Department of Environmental and Occupational Health, College of Public Health, China Medical University, Shenyang, Liaoning 110001, PR China
b
Shenyang Medical College, Shenyang, Liaoning, PR China
Received 16 June 2005; received in revised form 13 November 2005; accepted 22 November 2005
Available online 2 February 2006
Abstract
The primary goal of the present study was to confirm the arsenic species that can be transferred from the mother to the bodies of
newborn pups through the placenta and the speciated arsenic distribution in the liver and brain of newborn mice after gestational
maternal exposure to inorganic arsenic (iAs). Mother mice were exposed to iAsIII and iAsV in drinking water during gestation. The
livers and brains of the mother mice and their newborn pups were taken. Contents of iAs, monomethylarsonic acid (MMA),
dimethylarsinic acid (DMA), and trimethylarsenic (TMA) compound were detected using the HG-AAS method. Contents of iAs, MMA,
and DMA in the liver of mother mice increased with the concentration of arsenite or arsenate in their drinking water. However, only
DMA increased with the concentration of arsenate or arsenite in the drinking water in the brain of mother mice. On the other hand,
contents of both iAs and DMA in the liver and brain of newborn mice increased with the concentration of arsenate or arsenite
administered to their mother orally. Contents of arsenic species in the liver and brain of both mother mice and their newborn pups were
significantly lower in the 10 ppm iAsV group than in the 10 ppm iAsIII group. Ratios of iAs or DMA levels between the brain and the
liver of newborn mice were larger than 1, whereas those in mother mice were much smaller than 1. iAs taken from drinking water was
distributed and metabolized mainly in the liver of mother mice. iAsIII in low levels may be taken up and metabolized easily in the liver
compared to iAsV. Both iAs and DMA are transferred from the mother through the placenta and cross the immature blood–brain
barrier (BBB) easily. Compared to that in the liver of newborn mice, DMA as an organic metabolite is prevalent in brain, a lipidic organ,
if the BBB is not matured enough to prevent it from entering the brain.
r 2006 Elsevier Inc. All rights reserved.
Keywords: Arsenic species; Methylation; Mice; Disposition; Repeated exposure; Metabolism; Arsenite; Arsenate
1. Introduction
Arsenic is one of the most important global environmental toxicants. Drinking water is the main source of
arsenic in most human populations, where inorganic forms
of arsenic predominate (Pott et al., 2001; Waalkes et al.,
2004). The two main forms of inorganic arsenic (iAs) found
in the drinking water are arsenate (iAsV) and arsenite
(iAsIII). They are absorbed efficiently through the gastrointestinal tract and distributed in organs after the first pass
through the liver. iAs taken up through the first pass is
Corresponding author.
E-mail address: [email protected] (G. Sun).
0013-9351/$ - see front matter r 2006 Elsevier Inc. All rights reserved.
doi:10.1016/j.envres.2005.11.006
metabolized in liver of humans and most rodents to
monomethylarsonic acid (MMA) and dimethylarsinic acid
(DMA) by consecutive reduction and oxidative methylations (Aposhian, 1997; Thomas et al., 2001; Kitchin, 2001).
Although the methylation of iAs has long been considered
as a detoxification mechanism (Buchet et al., 1981; Vahter
and Marafante, 1983), the metabolites of toxic methylated
trivalent arsenicals make it as an intoxication process
(Thomas et al., 2004; Dopp et al., 2004; Mass et al., 2001).
Waalkes et al. (2003, 2004) reported that maternal oral
exposure to iAs during gestation in mice resulted in a
strong carcinogenic response in the offspring after they had
become adults. Recent studies indicated that DMA
treatment can cause tumor promotion or act as a complete
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Y. Jin et al. / Environmental Research 101 (2006) 349–355
carcinogen (Morikawa et al., 2000; Yamanaka et al., 2000,
2001; Wei et al., 2002; Salim et al., 2003). However,
humans are not exposed to DMA directly because
methylated species would rarely occur in drinking water.
Because DMA is generated from iAs in humans and
rodents, a better understanding of the disposition of
arsenic species at target organs will aid in gaining insight
into the arsenic induced toxicity and reduce the uncertainty
in the risk assessment for this metalloid.
Gestation in humans and rodents is a period of high
sensitivity to chemical toxicity (Anderson et al., 2000;
Tomatis et al., 1992). Studies showed that after administration of iAs during gestation the metalloid can readily
cross the human and animal placenta and enter the fetal
system (Chattopadhyay et al., 2002; Concha et al., 1998).
Because the toxicity or carcinogenesis of arsenic depends
on its chemical forms as well as oxidative states (Cullen and
Reimer, 1989; Mandal et al., 2004), forms of this
transplacental toxicant in biological samples of fetuses or
pups is an essential tool to gain insight into its distribution
in tissues and its species-specific toxicity to their target
organs.
The health risks to children, especially on intellectual
impairment from environmental arsenic exposure received
increasing concerns in recent years (Fujino et al., 2004;
Tsuji et al., 2004, Watanabe et al., 2003). Wasserman et al.,
(2004) disclosed that water iAs was associated with reduced
intellectual function, in a dose–response manner, such that
children with water iAs levels 450 mg/L achieved significantly lower Performance and full-scale scores than did
children with water iAs levels o5.5 mg/L.It is well known
that the central nervous system (CNS) is more susceptible
to the toxic agents, such as lead or mercury exposed in the
early developmental stage. The questions arise as to exactly
how brain in its early developmental stage expose to the
species of arsenicals. Does it suffer a species similar to that
of the mother? Can all arsenic species pass the immature
blood–brain barrier (BBB) of new born pups freely?
Furthermore, arsenic conversion to DMA is not universal
in all cells, for example, the epidermal keratinocytes of
humans, a suspected target cell of arsenic in the skin, do
not form DMA upon exposure to iAs (Vega et al., 2001)
and methylation of arsenic take place chiefly in the liver
(Yamauchi and Yamamura, 1984). Therefore, the metabolic activity in the liver seems to control the distribution
of arsenic taken up by the gastrointestinal tract, and the
resulting chemical forms in organs affect the toxicity of
animals. Can iAs transported through placenta be metabolized in the liver of newborn pups? Thus, the primary
goal of the present study was to confirm the arsenic species
can be transferred from the mother to the bodies of
newborn pups through the placenta, and enter the liver or
brain of the newborn pup after gestational maternal
exposure to iAs. Though many studies have suggested that
arsenic freely passes the human and animal placenta, few
data could be used to assess transportation and distribution of arsenic speciation in liver and brain of newborn
pups during gestational maternal exposure to different
forms of iAs.
2. Methods
2.1. Chemicals
Arsenate (Na3AsO4 12H2O), arsenite (NaAsO2), HCl, NaOH and
NaBH4 were purchased from the Shanghai Chemical Co. (Shanghai, PR
China). All reagents used in this study are analytical grade and arsenic free
(smaller than 0.01 ppm), the highest grade commercially available in
China. Mixed Standard reference materials of MMA, DMA and TMA
were obtained from Tri Chemical Laboratories Inc. (Yamanashi, Japan),
which contain 1000 ppm of MMA, DMA and TMA, respectively.
Standard reference materials of iAs (GBW 08611) was obtained from
the national center for standard reference materials (Beijing, China),
which contain 1000 ppm of iAs. Standard Reference Material of Dried
Oyster Tissue (SRM1566b) for metals was obtained from the US National
Institute of Standards and Technology (Gaithersburg, MD).
2.2. Animals
Albino mice, weighing 2672 g, were obtained from the animal
laboratory of China Medical University. All animal experiments were
approved by the Institutional Animal Care and Use Committees of China
Medical University. The animal room was kept at a temperature of
2072 1C with a 12 h light/dark cycle and a relative humidity of 50–60%.
Free access to food and water was allowed at all the time. The animals
were initially housed 5 per cage in the sterilized plastic cages with wood
shaving bedding. After 1-week adaptation, female mice were mated with
healthy male mice. Gestation was determined by checking vaginal plug
and vaginal smears twice daily (AM and PM). Conception was estimated
by vaginal plug or sperm positive. Pregnant mice in experimental groups
were feed separately (one per cage) and given drinking water in which
arsenite or arsenate was dissolved in redistilled water to the desired
concentrations expressing as parts per million (ppm). The concentrations
of arsenic in trivalent or pentavalent form were 10 and 30 ppm,
respectively. A total of 17.3, 52.0 mg of NaAsO2 or 56.5, 169.0 mg of
Na3AsO4 12H2O was dissolved in 1 of redistilled water, respectively, and
newly made every 24 h to keep most part of arsenic in arsenite
administered water in trivalent form.
2.3. Grouping
Five groups with six pregnant mice per group were divided randomly
by the time sequence of gestation. They were groups of 10 and 30 ppm of
iAsIII and 10 and 30 ppm iAsV and control. The pregnant mice in the
treated groups drank redistilled water added with different concentrations
and forms of iAs ad libitum from the first day of gestation and the
pregnant mice in control drank redistilled water.
2.4. Procedure
Newborn mice were taken one per liter immediately after parturition,
and then the liver and brain were exenterated. The mother mice drank
water contaminated with arsenic continually in lactation, and were
sacrificed at the end of lactation. Their liver and brain were removed
immediately. All these organs were kept in 20 1C for analysis of arsenic
species.
2.5. Analytical method
Determination of arsenic species (iAs, MMA, DMA and TMA) in
tissue was performed by using the equipment of atomic absorption
spectrophotometer (AA-6800) with a arsenic speciation pretreatment
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Y. Jin et al. / Environmental Research 101 (2006) 349–355
system (ASA-2SP), Shimadzu Co. Kyoto, Japan. Method described by
Yamauchi and Yamamura (1984) was followed with slight modification.
Briefly, 0.1 g of liver or brain from mother mice or their pups was digested
with 4 N NaOH solution at 100 1C for 3 h in a 10 mL polymethylpentene
test tube, and then were diluted with redistilled water. Digested solution
were assayed using the method based on the hydride generation of volatile
arsines, followed by cryogenic separation (in liquid nitrogen) and final
detection of arsine, methyl-, dimethyl- and trimethyl-arsine was by atomic
absorption spectrophotometry (HGAAS). Arsenic was detected at
193.3 nm. This method, done at pH o2, generated arsines from both
tri- and pentavalent arsenicals and cannot distinguish whether the
arsenicals in the samples are in the trivalent or pentavalent form. Quality
control for arsenic determinations included the analysis of SRM1566b.
The certified concentration values of arsenic were 7.6570.65 mg/g. The
values measured in present laboratory were almost the same. The precision
in consecutive measurements of this method was satisfactory as the
coefficient of variation (CV) within the same day and between days was all
within 5%. The reliability of arsenic species separation was checked by the
analytical recoveries of added arsenic species. Spiking control liver and
brain samples with known amounts of iAs, MMA, DMA and TMA
(10 ppb, respectively) was assessed, and the recoveries of iAs, MMA,
DMA and TMA were 80–90%, 84–95%, 88–96% and 88–103%,
respectively. Using this method, the detection limit of each of the four
chemical species of arsenic was 1 ng. Because TMA in the liver of mother
mice were not significant among groups and not detected in the brain of
mother mice and in both liver and brain of newborn mice, the total arsenic
species (TAs) was determined to be the sum of (iAs+MMA+DMA).
2.6. Statistical analysis
Data are presented as means7SD. Nonparametric test of Kruskal–
Wallis test was used for analysis by SPSS software (version 11.5, SPSS
Inc., Chicago, IL, USA). After nonparametric analysis, parametric test of
One-way ANOVA was done on the rank sequence of the data, and
Student–Newman–Keuls (SNK) of post hoc test was employed. The mean
difference is significant at the 0.05 level.
3. Results
The doses of arsenic used in present study were well
tolerated and did not alter maternal water consumption,
maternal body weight or body weights of the newborn
pups.
351
In Fig. 1, the selected typical spectra of arsines detected
in the liver and brain of mother mice and their newborn
pups was shown. Picture A depicted the standard spectra of
arsenic species, peaks a–d represented the spectrum of iAs,
MMA, DMA and TMA, respectively. Pictures B and D
depicted the spectra of arsenic species in the liver and brain
of mother mice in control. Picture C and E depicted the
spectra of arsenic species in the liver and brain of mother
mice in group of 30 ppm iAsIII. Pictures F and G depicted
the spectra of arsenic species in the liver and brain of
newborn mice in group of 30 ppm iAsIII. In picture B, peak
a and d was shown, which suggested that iAs and TMA
was detected in the liver of mother mice in control; in
picture C, peaks a–d were all shown, suggested iAs, MMA,
DMA and TMA were detected in the liver of mother mice
in group of 30 ppm iAsIII; in picture D, peak a was shown,
suggested only iAs was detected in the brain of mother
mice in control; in picture E, peaks a and c were shown,
suggested iAs and DMA were detected in brain of mother
mice in group of 30 ppm iAsIII, however, compared to that
in control, only the DMA was increased significantly;
however, in pictures F and G, both iAs and DMA were
increased significantly.
In Fig. 2A, comparison of levels of arsenic species in the
liver of mother mice was shown. Levels of iAs in group of
10 ppm iAsIII or 30 ppm iAsIII or iAsV were higher
significantly than in control or group of 10 ppm iAsV.
Levels of MMA in group of 10 ppm iAsIII or 30 ppm
iAsIII or iAsV were higher significantly than in control or
group of 10 ppm iAsV, and in group of 30 ppm iAsIII or
iAsV were higher significantly than in group of 10 ppm
iAsIII. Levels of DMA in group of 10 ppm iAsIII or
30 ppm iAsIII or iAsV were significantly higher than in
control, and in group of 30 ppm iAsIII and iAsV were
higher significantly than in group of 10 ppm iAsIII or iAsV.
Levels of TAs in group of 10 ppm iAsIII or iAsV or 30 ppm
iAsIII or iAsV were higher significantly than in control, in
group of 10 ppm iAsIII or 30 ppm iAsIII or iAsV were
Fig. 1. Typical spectra of arsenic speciation: (A) depicted the standard spectra of arsenic speciation, (a, iAs; b, MMA; c, DMA; d, TMA), (B) depicted the
spectra of arsenic speciation in liver of mother mice in control, (C) depicted the spectra of arsenic speciation in liver of mother mice in group of 30 ppm
iAsIII, (D) depicted the spectra of arsenic speciation in brain of mother mice in control, (E) depicted the spectra of arsenic speciation in brain of mother
mice in group of 30 ppm iAsIII, (F) depicted the spectra of arsenic speciation in liver of newborn mice in group of 30 ppm iAsIII, (G) depicted the spectra
of arsenic speciation in brain of newborn mice in group of 30 ppm iAsIII.
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Y. Jin et al. / Environmental Research 101 (2006) 349–355
Concentrations
(µg As/g wet w.t.)
352
1.4
Control
1.2
10ppm iAsIII
*
*
10ppm iAsV
1.0
30ppm iAsIII
0.8
0.6
0.4
*
30ppm iAsV
*
*
*
*
* *
*
**
*
*
0.2
0.0
iAs
Concentrations
(µg As/g wet w.t.)
(A)
MMA
0.35
Control
0.30
10ppm iAsIII
0.25
10ppm iAsV
0.20
30ppm iAsIII
0.15
30ppm iAsV
DMA
Groups
TMA
TAs
* *
* *
0.10
*
*
*
0.05
0.00
iAs
(B)
MMA
DMA
Groups
TMA
TAs
Concentrations
(µg As/g wet w.t.)
Fig. 2. Concentrations of arsenic species in the liver (A) and brain (B) of mother mice. (Notes: bars represented mean7standard deviation. iAs: inorganic
arsenic, MMA: monomethylarsonic acid, DMA: dimethylarsinic acid, TMA: trimethylarsenic compound, Total concentration of arsenicals
(TAs) ¼ iAs+MA+DMA. The asterisk (*) indicated arsenic concentration at specific group was significant as comparing with the other groups. The
significant levels was at 0.05. The number of mother mice in each group was 6.)
0.35
Control
0.30
10ppm iAsIII
0.25
10ppm iAsV
0.20
30ppm iAsIII
0.15
30ppm iAsV
*
*
0.05
* *
*
iAs
MMA
DMA
Groups
(A)
Concentrations
(µg As/g wet w.t.)
*
0.10
0.00
0.35
Control
0.30
10ppm iAsIII
0.25
10ppm iAsV
0.20
0.15
0.10
30ppm iAsIII
0.05
*
TMA
TAs
* *
*
*
*
30ppm iAsV
*
*
* *
*
0.00
iAs
(B)
*
*
*
MMA
DMA
Groups
TMA
TAs
Fig. 3. Concentrations of arsenic species in liver (A) and brain (B) of newborn mice. (Notes: bars represented mean7standard deviation. iAs: inorganic
arsenic, MMA: monomethylarsonic acid, DMA: dimethylarsinic acid, TMA: trimethylarsenic compound, Total concentration of arsenicals
(TAs) ¼ iAs+MA+DMA. The asterisk (*) indicated arsenic concentration at specific group was significant as comparing with the other groups.
Significant levels was at 0.05. The number of newborn mice in each group was 6.)
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Y. Jin et al. / Environmental Research 101 (2006) 349–355
higher significantly than in group of 10 ppm iAsV, and in
group of 30 ppm iAsIII or iAsV were higher significantly
than in group of 10 ppm iAsIII. Levels of TMA were not
significant among groups.
In Fig. 2B, comparison of levels of arsenic species in the
brain of mother mice was shown. Levels of iAs in group of
30 ppm iAsIII were significantly higher than in control or
group of 10 ppm iAsV. Levels of DMA in group of 10 ppm
iAsIII or 30 ppm iAsIII or iAsV were significantly higher
than in control, and in group of 30 ppm iAsIII or iAsV
were higher significantly than in group of 10 ppm iAsV.
Levels of TAs in group of 10 ppm iAsIII or 30 ppm iAsIII
or iAsV were significantly higher than in control or group
of 10 ppm iAsV, and in group of 30 ppm iAsIII or iAsV
were significantly higher than in group of 10 ppm iAsIII.
In Fig. 3A, comparison of levels of arsenic species in the
liver of newborn mice was shown. Levels of iAs in group of
10 ppm iAsIII or 30 ppm iAsIII or iAsV were higher
significantly than in control. Levels of DMA in group of
10 ppm iAsIII or 30 ppm iAsIII or iAsV were significantly
higher than in control or group of 10 ppm iAsV. Levels of
TAs in group of 10 ppm iAsIII or 30 ppm iAsIII or iAsV
were significantly higher than in control or group of
10 ppm iAsV.
In Fig. 3B, comparison of levels of arsenic species in the
brain of newborn mice was shown. Levels of iAs in group
of 10 ppm iAsIII or 30 ppm iAsIII or iAsV were higher
significantly than in control or group of 10 ppm iAsV.
Levels of MMA in group of 30 ppm iAsV were higher
significantly than in control or group of 10 ppm iAsIII or
iAsV. Levels of DMA in group of 10 ppm iAsIII or 30 ppm
iAsIII or iAsV were higher significantly than in control or
group of 10 ppm iAsV. Levels of TAs in group of 10 ppm
iAsIII or 30 ppm iAsIII or iAsV were higher significantly
than in control or group of 10 ppm iAsV, and in group of
10 ppm iAsV were higher significantly than in control.
Levels of TMA were under the detected limitation in the
brain of mother mice and in both liver and brain of
newborn mice. Levels of iAs, MMA, DMA and TAs were
not significant between groups of 30 ppm iAsV and iAsIII
in both liver and brain of mother and newborn mice.
4. Discussion
Arsenic is excreted primarily in urine by most mammalian species, the analysis of urine collected from humans
and animals exposed to the high levels of iAs is the primary
way of studying iAs metabolism in vivo, and DMA is the
main product eliminated in urine. However, the use of
metabolite data in urine as the surrogate for arsenic species
in tissue is a significant uncertainty in risk assessment
because it may not adequately reflect target tissue
distribution (Kenyon et al., 2005a, b; Rodriguez et al.,
2005; Hughes et al., 2003). The study reported by Kenyon
et al. (2005a) clearly demonstrated that levels of arsenic
species in tissues were both tissue specific and dose
dependent. Based on their data, it appeared that speciated
353
urinary arsenic levels adequately reflected speciated lung
arsenic levels, but not speciated arsenic levels in blood, liver
or kidney.
Although the health risks to children, especially on
intellectual impairment from environmental arsenic exposure received increasing concerns in recent years, there are
few previous studies relating the arsenical exposure to the
presence of arsenic species in brain, which could be in to
some extent responsible for the neurotoxic alterations
reported (Rodriguez et al., 2005). A variety of mammalian
species, including the human, have been shown to be
susceptible to the embryo toxic effects of iAs. The CNS
may be especially vulnerable during its early development.
To our knowledge, this is the first study on the distribution
of arsenic species in the liver and brain of newborn mice
exposed iAs through mother orally.
In present study, levels of iAs, MMA and DMA in the
liver of mother mice increased with the levels of arsenite or
arsenate in their drinking water. Levels of sumation of
arsenic species were much higher than those in the brain of
mother mice and in both brain and liver of newborn mice.
Though TMA was also detected in the liver of mother
mice, it was not significant among groups. Thus, it was
speculated that TMA detected in present study might be
taken up from the seafood added in the feedstuff. Several
studies have demonstrated that, compared to the other
organs such as lung and kidney, liver is the primary arsenic
methylating organ, and DMA was the major end product
of arsenic methylation (Hughes et al., 2003; Kitchin et al.,
1999). The results of the present study corroborate that iAs
taken up orally were mainly accumulated and metabolized
in the liver of mother mice, and DMA is the predominant
metabolite of iAs in mice. Our findings in the liver of
mother mice also showed that levels of arsenic species in
group of 10 ppm iAsV were much lower than in group of
10 ppm iAsIII. Similar results were also found in the brain
of mother mice and in both liver and brain of newborn
mice. A comparison of 24 h cumulative urinary metabolites
of mice administered 100 mmol As/kg of arsenate or
arsenite indicated there was a difference in the metabolic
profile (Kenyon et al., 2005b). A lower percentage of DMA
(60%) was excreted in urine in arsenate-treated mice
compared to arsenite-treated mice (80%). The data
reported by Cui et al. (2004) showed that 43% of DMA,
47% of iAsIII, and 10% of iAsV were detected in urine of
iAsIII intravenously (iv) exposed rats, whereas only 3% of
DMA, 87% of iAsV, and 10% of iAsIII were detected in
urine of the same doses of iAsV-iv exposed rats. These
indicated that arsenite is more easily methylated than
arsenate, perhaps because of greater uptake into tissues
that arsenic methylated. Styblo et al. (1995) showed in rat
hepatic cytosol that 90% of arsenite is methylated to
dimethyl arsenic, whereas only 40% of arsenate is
methylated during a 90 min incubation. All these data
suggested that reduction of arsenate to arsenite might be
the rate limiting step (arsenite directly and arsenate after
reduction to arsenite). On the other hand, no significant
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Y. Jin et al. / Environmental Research 101 (2006) 349–355
differences of levels of arsenic species between groups of
30 ppm iAsIII and iAsV might reflect either saturation or
inhibition of methylation. Study reported by Kenyon et al.
(2005b) showed that as the amount of arsenite administered increased, the percentage of DMA excreted in urine
decreased. There was a concomitant increase in the
percentage of iAs and MMA excreted with increasing dose
of arsenite. They suggested that the methylation of arsenite
and MMA was either inhibited or saturated with increased
dose of administered arsenite.
Compared to those in the liver of mother mice, sumation
of arsenic species in the brain of mother mice were much
lower, and only levels of DMA increased with the levels of
arsenite or arsenate in their drinking water, which
suggested that transport of arsenic species to the brain of
mother mice may be limited by the matured BBB. The
mechanism for the DMA distributed in brain is not known.
However, study reported recently by Rodriguez et al.
(2005) showed that MMA and DMA could be formed in
brain from iAs by incubating brain slices with sodium
arsenite. Thus DMA in the brain might either be formed in
the liver from iAs and then transported to the brain, or
alternatively, that iAs was transported to the brain and
then methylated to DMA.
Compared to those in the brain of mother mice,
sumation of arseinc species in the brain or liver of newborn
mice was higher, and the levels of both iAs and DMA
increased with the levels of arsenite or arsenate in their
mother’s drinking water, which may suggest that iAs and
its methylated metabolites could pass through placenta
barrier easily. However, compared to those in the liver of
newborn mice, levels of iAs in brain were nearly the same
(1:1), and levels of DMA in brain were much higher (1:2).
So it is reasonable to speculate that DMA as an organic
metabolite might accumulate preferentially in brain, a
lipidic organs, although it might either be transported to
the brain, or alternatively, that iAs was transported to the
brain and then methylated to DMA, if the BBB was not
matured enough to limite them from entering. Study
reported by Concha et al. (1998) showed that concentration of arsenic in cord blood (median, 9 mg/L) was almost
as high as in maternal blood (median, 11 mg/L), and there
was a significant correlation between the two, which
suggested in gestation arsenic is easily transferred to the
fetus. Furthermore, their data showed that arsenic species
in the blood of both the newborns and their mothers was in
the form of DMA, which indicated that DMA is the major
form of arsenic transferred from mothers to their fetuses.
In our previous study (Jin et al. 2004), we found that
pentavalent methylated arsenicals, i.e. MMAV and
DMAV, have no toxic effects, however inorganic arsenicals, iAsIII and iAsV showed obvious toxic effects on
primary cultured astroglia at micromolar concentrations.
Petrick et al. (2000) reported that DMAV is lethal to
cultured human hepatocytes, though its toxicity three
orders of magnitude lower than iAsIII or MMAIII. The
data reported by Namgung and Xia (2001) also showed
that DMAV was about three orders of magnitude less
potent than iAsIII in inducing apoptosis in cerebellum
neurons. Taken together, though the DMAV is relatively
toxic, both iAs and DMA are toxic to the neurons and
neuroglia in the brain tissue. On the other hand, although
the methodology employed in present study to determine
arsenic species cannot ascertain if they are in their trivalent
or pentavalent form, it can be assumed that methylated
trivalent species can be found in the liver and brain of both
mother and newborn mice. Because of the high affinity of
trivalent methylated arsenicals to sulfhydryl groups, these
organic trivalent forms, MMAIII and DMAIII, are more
toxic than their pentavalent counterparts or iAs (Petrick
et al., 2000, 2001; Styblo et al., 2000). As the sumation of
arsenic species and levels of DMA or iAs in the brain
of newborn mice were more higher than those in the brain
of mother mice, we could speculate that brain of newborn
mice may suffer more toxic effects induced by arsenic
exposure.
Acknowledgments
This study was funded by the National Natural Scientific
foundation of China. The project numbers are 30571590
and 30530640.
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