# Environmental Arsenic Exposure and Hematotoxicity

> **NIH NIH R16** · NEW MEXICO HIGHLANDS UNIVERSITY · 2022 · $185,625

## Abstract

Project Summary
Anemia adversely impacts the health of more than a billion people worldwide. A strong
association between anemia and arsenic (As) exposure has been reported in epidemiological
studies from multiple countries. However, the mechanistic bases for the association between As
exposure and anemia is not fully understood. Previous research by our group provides evidence
of arsenic hematotoxicity spanning from humans to mouse models. Our previous work focused
on establishing the role of inorganic arsenite (As3+) as a hematotoxicant, particularly by
determining the effects of As3+ on the zinc finger transcription factor GATA-1, which is essential
for normal red blood cell (RBC) development (i.e. erythropoiesis). Based on this work, we found
that As exposure causes anemia via the suppression of early erythroid progenitor cell
development. We provide further evidence that this inhibition of RBC development occurs as a
result of disruptions to GATA-1 function. These findings provide essential information regarding
a molecular mechanism of As-induced inhibition of erythropoiesis, but also highlight an area
requiring further investigation. Many studies suggest that the As3+ metabolite,
monomethylarsonous acid (MMA3+) may be the major form of As responsible for toxicity
observed in vivo; however, few studies have been performed to directly evaluate the role of As
metabolism in the tissue distribution of arsenicals and subsequent toxicity at these sites. The
proposed Focus Research Project will provide novel information regarding the role of As
metabolism as a potential mediator of the observed hematotoxicity. The studies proposed in
Aim 1 will address this important knowledge gap by examining the role of As metabolites in the
hematotoxicity observed following As3+ and MMA3+ exposures, in vivo and in vitro. Aim 2 will
investigate mechanisms of As metabolism-mediated inhibition of erythropoiesis by comparing
the effects of As3+ to MMA3+ on important protein regulators of erythropoiesis. Outcomes from
the proposed research will provide critical information essential for understanding the role of As
metabolism in As-associated anemias and other hematological disorders.

## Key facts

- **NIH application ID:** 10497102
- **Project number:** 1R16GM146669-01
- **Recipient organization:** NEW MEXICO HIGHLANDS UNIVERSITY
- **Principal Investigator:** Sebastian Medina
- **Activity code:** R16 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $185,625
- **Award type:** 1
- **Project period:** 2022-08-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10497102

## Citation

> US National Institutes of Health, RePORTER application 10497102, Environmental Arsenic Exposure and Hematotoxicity (1R16GM146669-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10497102. Licensed CC0.

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