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Carcinogenic metals and the epigenome: understanding the effect of nickel, arsenic, and chromium.

Metallomics : integrated biometal science (2012-04-05)
Yana Chervona, Adriana Arita, Max Costa
ABSTRACT

Carcinogenic metals, such as nickel, arsenic, and chromium, are widespread environmental and occupational pollutants. Chronic exposure to these metals has been connected with increased risks of numerous cancers and as well as non-carcinogenic health outcomes, including cardiovascular disease, neurologic deficits, neuro-developmental deficits in childhood, and hypertension. However, currently the specific molecular targets for metal toxicity and carcinogenicity are not fully understood. Here, we propose that the iron- and 2-oxoglutarate-dependent dioxygenase family enzymes, as well as, other histone modifying enzymes are important intracellular targets that mediate the toxicity and carcinogenicity of nickel, and maybe potential targets in chromium and arsenic induced carcinogenesis. Our data demonstrate that all three metals are capable of inducing post-translational histone modifications and affecting the enzymes that modulate them (i.e. the iron- and 2-oxoglutarate-dependent dioxygenase family, including HIF-prolyl hydroxylase PHD2, histone demethylase JHDM2A/JMJD1A, and DNA repair enzymes ABH3 and ABH2, and histone methyltransferases, G9a). Given the effects that these metals can exert on the epigenome, future studies of their involvement in histone modifying enzymes dynamics would deepen our understanding on their respective toxicities and carcinogenicities.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Chromium, chips, 99.995% trace metals basis
Sigma-Aldrich
Chromium, powder, ≥99% trace metals basis, <45 μm
Sigma-Aldrich
Chromium, powder, 99.5%, −100 mesh
Sigma-Aldrich
Chromium, chips, thickness ~2 mm, 99.5%
Chromium, foil, light tested, 25x25mm, thickness 0.05mm, permanent polyester support, 99.99+%
Chromium, foil, light tested, 25x25mm, thickness 0.075mm, permanent polyester support, 99.99+%
Chromium, foil, not light tested, 100x100mm, thickness 0.0125mm, permanent polyester support, 99.99+%
Chromium, foil, not light tested, 100x100mm, thickness 0.015mm, permanent polyester support, 99.99+%
Chromium, foil, not light tested, 100x100mm, thickness 0.01mm, permanent polyester support, 99.99+%
Chromium, foil, not light tested, 100x100mm, thickness 0.025mm, permanent polyester support, 99.99+%
Chromium, foil, not light tested, 100x100mm, thickness 0.02mm, permanent polyester support, 99.99+%
Chromium, foil, not light tested, 100x100mm, thickness 0.03mm, permanent polyester support, 99.99+%
Chromium, foil, not light tested, 100x100mm, thickness 0.04mm, permanent polyester support, 99.99+%
Chromium, foil, not light tested, 25x25mm, thickness 0.0015mm, permanent polyester support, 99.99+%
Chromium, foil, not light tested, 25x25mm, thickness 0.001mm, permanent polyester support, 99.99+%
Chromium, foil, not light tested, 25x25mm, thickness 0.0025mm, permanent polyester support, 99.99+%
Chromium, foil, not light tested, 25x25mm, thickness 0.002mm, permanent polyester support, 99.99+%
Chromium, foil, not light tested, 25x25mm, thickness 0.003mm, permanent polyester support, 99.99+%
Chromium, foil, not light tested, 25x25mm, thickness 0.004mm, permanent polyester support, 99.99+%
Chromium, foil, not light tested, 25x25mm, thickness 0.005mm, permanent polyester support, 99.99+%
Chromium, foil, not light tested, 25x25mm, thickness 0.007mm, permanent polyester support, 99.99+%
Chromium, foil, not light tested, 25x25mm, thickness 0.009mm, permanent polyester support, 99.99+%
Chromium, foil, not light tested, 25x25mm, thickness 0.0125mm, permanent polyester support, 99.99+%
Chromium, foil, not light tested, 25x25mm, thickness 0.015mm, permanent polyester support, 99.99+%
Chromium, foil, not light tested, 25x25mm, thickness 0.01mm, permanent polyester support, 99.99+%
Chromium, foil, not light tested, 25x25mm, thickness 0.025mm, permanent polyester support, 99.99+%
Chromium, foil, not light tested, 25x25mm, thickness 0.03mm, permanent polyester support, 99.99+%
Chromium, foil, not light tested, 25x25mm, thickness 0.04mm, permanent polyester support, 99.99+%
Chromium, foil, not light tested, 25x25mm, thickness 0.05mm, permanent polyester support, 99.99+%
Chromium, foil, not light tested, 25x25mm, thickness 0.075mm, permanent polyester support, 99.99+%