Autophagy is the predominant process induced by arsenite in human lymphoblastoid cell lines

Journal Article · Sat May 01 00:00:00 EDT 2010 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2010.01.019· OSTI ID:21344939

Bolt, Alicia M; Byrd, Randi M ^[1]

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1. Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ 85724 (United States)

Arsenic is a widespread environmental toxicant with a diverse array of molecular targets and associated diseases, making the identification of the critical mechanisms and pathways of arsenic-induced cytotoxicity a challenge. In a variety of experimental models, over a range of arsenic exposure levels, apoptosis is a commonly identified arsenic-induced cytotoxic pathway. Human lymphoblastoid cell lines (LCL) have been used as a model system in arsenic toxicology for many years, but the exact mechanism of arsenic-induced cytotoxicity in LCL is still unknown. We investigated the cytotoxicity of sodium arsenite in LCL 18564 using a set of complementary markers for cell death pathways. Markers indicative of apoptosis (phosphatidylserine externalization, PARP cleavage, and sensitivity to caspase inhibition) were uniformly negative in arsenite exposed cells. Interestingly, electron microscopy, acidic vesicle fluorescence, and expression of LC3 in LCL 18564 identified autophagy as an arsenite-induced process that was associated with cytotoxicity. Autophagy, a cellular programmed response that is associated with both cellular stress adaptation as well as cell death appears to be the predominant process in LCL cytotoxicity induced by arsenite. It is unclear, however, whether LCL autophagy is an effector mechanism of arsenite cytotoxicity or alternatively a cellular compensatory mechanism. The ability of arsenite to induce autophagy in lymphoblastoid cell lines introduces a potentially novel mechanistic explanation of the well-characterized in vitro and in vivo toxicity of arsenic to lymphoid cells.

• OSTI ID: 21344939
• Journal Information: Toxicology and Applied Pharmacology, Vol. 244, Issue 3; Other Information: DOI: 10.1016/j.taap.2010.01.019; PII: S0041-008X(10)00046-3; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
ARSENIC
FLUORESCENCE
IN VITRO
IN VIVO
LYMPHOCYTES
MEN
SODIUM COMPOUNDS
TOXICITY
TRANSMISSION ELECTRON MICROSCOPY
ALKALI METAL COMPOUNDS
ANIMAL CELLS
ANIMALS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CONNECTIVE TISSUE CELLS
ELECTRON MICROSCOPY
ELEMENTS
EMISSION
LEUKOCYTES
LUMINESCENCE
MALES
MAMMALS
MAN
MATERIALS
MICROSCOPY
PHOTON EMISSION
PRIMATES
SEMIMETALS
SOMATIC CELLS
VERTEBRATES