cn9b00653_si_001.pdf (180.91 kB)
Comparative Cytotoxicity of Inorganic Arsenite and Methylarsenite in Human Brain Cells
journal contribution
posted on 2020-02-12, 12:33 authored by Kunie Yoshinaga-Sakurai, Ravikumar Shinde, Myosotys Rodriguez, Barry P. Rosen, Nazira El-HageThe overall goal
of this study is to elucidate the potential effect(s) of arsenic on
a variety of human brain cells. Arsenic is the most pervasive Group
A human environmental carcinogen. Long-term exposure to arsenic is
associated with human diseases including cancer, cardiovascular disease,
and diabetes. More immediate are the health effects on neurological
development and associated disorders in infants and children exposed
to arsenic in utero. Arsenic is metabolized in various
organs and tissues into more toxic methylated species, including methylarsenite
(MAs(III)), so the question arises whether the methylate species are
responsible for the neurological effects of arsenic. Arsenic enters
the brain through the blood–brain barrier and produces toxicity
in the brain microvascular endothelial cells, glia (astrocytes and
microglia), and neurons. In this study, we first assessed the toxicity
in different types of brain cells exposed to either inorganic trivalent
As(III) or MAs(III) using both morphological and cytotoxicity cell-based
analysis. Second, we determined the methylation of arsenicals and
the expression levels of the methylation enzyme, As(III) S-adenosylmethionine
(SAM) methyltransferase (AS3MT), in several types of brain cells.
We showed that the toxicity to neurons of MAs(III) was significantly
higher than that of As(III). Interestingly, the differences in cytotoxicity
between cell types was not due to expression of AS3MT, as this was
expressed in neurons and glia but not in endothelial cells. These
results support our hypothesis that MAs(III) is the likely physiological
neurotoxin rather than inorganic arsenic species.