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Arsenic is an environmental toxicant and a human carcinogen,
but paradoxically it has therapeutic effects too. A field
survey, conducted amongst the inhabitants of north 24 Parganas,
West Bengal, exposed to arsenic, shows the prevalence of
different types of arsenic induced skin lesions at exposure
to low non-toxic doses. The results reveal a significant
preponderance of dermal effects like hyperkeratosis and
raindrop pigmentation at low doses; however, little correlation
was observed with the arsenic exposure and arsenic level
in hair, nail or urine of the exposed subjects. Paradoxically,
in vitro application of the soluble most toxic and naturally
prevalent form of arsenic, sodium arsenite (NaAsO2), results
in a different outcome in human malignant melanoma cell
A375. Interestingly, 2 µM NaAsO2, the maximum dose
that can be achieved in blood plasma, led to induction of
apoptosis at 72 h of treatment, confirmed through Annexin
V-PI dual staining and DNA content analysis. Increase in
reactive oxygen species (ROS) production, loss of mitochondrial
membrane potential, associated with an activation of caspases
were found to be the critical mediators of apoptosis. Thus,
while chronic exposure to low doses of arsenic results in
dermal pathological symptoms in arsenic-exposed subjects;
application of similar concentration of arsenic in vitro
for 72 h results in apoptosis of malignant melanoma cells.
Arsenic is ubiquitous in the environment. Elevated concentrations
of arsenic over the past 20 years have given rise to increasing
concern due to mounting evidence of adverse human health
effects. For example, almost 50 million people are at risk
in Bangladesh where both chronic and acute arsenic poisoning
have been reported previously (Sengupta et al., 2003). The
World Health Organization (WHO), the Department of Health
and Human Services (DHHS), and the US Environmental Protection
Agency (EPA) have determined that inorganic arsenic is a
human carcinogen.
Arsenic
exposure has been associated with the development of various
types of cancer (Cantor and Lubin, 2007; Benbrahim-Tallaa
and Waalkes, 2008; and Vahter, 2008) exhibiting a clear predilection
for the skin (Fewtrell et al., 2005), which can be
potentially due to the high affinity of arsenic for sulfhydryl
groups leading to arsenic accumulation and retention in keratin-rich
skin tissue (Singh et al., 2007; and Tokunaga, 2007).
Since arsenic poisoning mostly occurs through the ingestion
of contaminated water and not by absorption of arsenic through
skin, it can be assumed that the amount of arsenic needed
to cause cytotoxicity would be higher in dermal fibroblasts
than in keratinocytes or melanocytes. It is thus anticipated
that the dose of arsenic lowers as it reaches the outer layer
of skin and hence, following ingestion, arsenic should affect
the innermost cells first. But in a study conveyed by Barbara
Graham-Evans group (Graham-Evans et al., 2003), it
was found that the LD50 for dermal fibroblasts was 187 µM,
45.5 µM for keratinocytes, compared to only 7.6 µM
for melanocytes, thus showing that arsenic is surprisingly
more toxic to melanocytes than dermal fibroblasts. Again,
data obtained so far from in vitro studies clearly
demonstrates that under similar exposure conditions, the mitogenicity,
cytotoxicity and diverse other cellular effects of arsenic
are dose and time-dependent and varies considerably (Bode
and Dong, 2002; and Huang et al., 2006). However, the
exact events on arsenic exposure still remain to be unraveled. |
