Record Information
Version2.0
Creation Date2009-06-19 21:58:46 UTC
Update Date2014-12-24 20:23:53 UTC
Accession NumberT3D1432
Identification
Common NameChromium(III) nitrate
ClassSmall Molecule
DescriptionChromium nitrate is a nitrate of chromium. It is used in the production of alkali metal-free catalysts and in pickling. Chromium is a chemical element which has the symbol Cr and atomic number 24. It is found naturally occuring in rocks, animals, plants, and soil, and is usually mined as chromite ore. Chromium is most toxic in its +6 oxidation state (chromiumNitrite is a toxic compound known to cause methemoglobinemia. (12)) due to its greater ability to enter cells and higher redox potential. Trivalent chromium (chromium(III)) however, is biologically necessary for sugar and lipid metabolism in humans. Nitrite is a toxic compound known to cause methemoglobinemia. (12, 7, 10)
Compound Type
  • Chromium Compound
  • Industrial/Workplace Toxin
  • Inorganic Compound
  • Nitrate
  • Nitrite
  • Pollutant
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
Chromium nitrate
Chromium(III) nitric acid
Nitric acid, chromium salt
Chemical FormulaCrN3O9
Average Molecular Mass238.011 g/mol
Monoisotopic Mass237.904 g/mol
CAS Registry Number13548-38-4
IUPAC Namechromium(3+) ion trinitrate
Traditional Namechromium(3+) ion trinitrate
SMILES[Cr+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O
InChI IdentifierInChI=1S/Cr.3NO3/c;3*2-1(3)4/q+3;3*-1
InChI KeyInChIKey=PHFQLYPOURZARY-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of inorganic compounds known as transition metal nitrates. These are inorganic compounds in which the largest oxoanion is nitrate, and in which the heaviest atom not in an oxoanion is a transition metal.
KingdomInorganic compounds
Super ClassMixed metal/non-metal compounds
ClassTransition metal oxoanionic compounds
Sub ClassTransition metal nitrates
Direct ParentTransition metal nitrates
Alternative Parents
Substituents
  • Transition metal nitrate
  • Inorganic oxide
  • Inorganic salt
Molecular FrameworkNot Available
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearancePurple crystals.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
logP0.028ChemAxon
pKa (Strongest Acidic)-1.4ChemAxon
pKa (Strongest Basic)-6.1ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area68.88 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity9.85 m³·mol⁻¹ChemAxon
Polarizability3.24 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
Toxicity Profile
Route of ExposureOral (6) ; inhalation (6) ; dermal (6)
Mechanism of ToxicityTrivalent chromium may also form complexes with peptides, proteins, and DNA, resulting in DNA-protein crosslinks, DNA strand breaks, DNA-DNA interstrand crosslinks, chromium-DNA adducts, chromosomal aberrations and alterations in cellular signaling pathways. It has been shown to induce carcinogenesis by overstimulating cellular regulatory pathways and increasing peroxide levels by activating certain mitogen-activated protein kinases. It can also cause transcriptional repression by cross-linking histone deacetylase 1-DNA methyltransferase 1 complexes to CYP1A1 promoter chromatin, inhibiting histone modification. Chromium may increase its own toxicity by modifying metal regulatory transcription factor 1, causing the inhibition of zinc-induced metallothionein transcription. Nitrate's toxicity is a result of it's conversion to nitrite once in the body. Nitrite causes the autocatalytic oxidation of oxyhemoglobin to hydrogen peroxide and methemoglobin. This elevation of methemoglobin levels is a condition known as methemoglobinemia, and is characterized by tissue hypoxia, as methemoglobin cannot bind oxygen. (5, 13, 1, 6, 2, 3, 4)
MetabolismChromium is absorbed from oral, inhalation, or dermal exposure and distributes to nearly all tissues, with the highest concentrations found in kidney and liver. Bone is also a major storage site and may contribute to long-term retention. Hexavalent chromium's similarity to sulfate and chromate allow it to be transported into cells via sulfate transport mechanisms. Inside the cell, hexavalent chromium is reduced first to pentavalent chromium, then to trivalent chromium by many substances including ascorbate, glutathione, and nicotinamide adenine dinucleotide. Chromium is almost entirely excreted with the urine. Intake of some amount of nitrates and nitrites is a normal part of the nitrogen cycle in humans. In vivo conversion of nitrates to nitrites can occur in the gastrointestional tract under the right conditions, significantly enhancing nitrates' toxic potency. The major metabolic pathway for nitrate is conversion to nitrite, and then to ammonia. Nitrites, nitrates, and their metabolites are excreted in the urine. (12, 1, 6)
Toxicity ValuesLD50: 3250 mg/kg (Oral, Rat) (11)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)Ingested nitrate or nitrite under conditions that result in endogenous nitrosation is probably carcinogenic to humans (Group 2A). Chromium (III) compounds are not classifiable as to their carcinogenicity to humans (Group 3). (8)
Uses/SourcesChromium nitrate is used in the production of alkali metal-free catalysts and in pickling. (10)
Minimum Risk LevelNot Available
Health EffectsChromium in its trivalent state is not very toxic. It may be oxidized to hexavalent chromium, a known carcinogen. Hexavalent chromium has also been shown to affect reproduction and development. Nitrate and nitrite poisoning causes methemoglobinemia. Nitrites may cause pregnancy complications and developmental effects. They may also be carcinogenic. (12, 1)
SymptomsChromium in its trivalent state is not very toxic, but it may be oxidized to hexavalent chromium. Breathing hexavalent chromium can cause irritation to the lining of the nose, nose ulcers, runny nose, and breathing problems, such as asthma, cough, shortness of breath, or wheezing. Ingestion of hexavalent chromium causes irritation and ulcers in the stomach and small intestine, as well as anemia. Skin contact can cause skin ulcers. Nitrate and nitrite poisoning causes methemoglobinemia. Symptoms include cyanosis, cardiac dysrhythmias and circulatory failure, and progressive central nervous system (CNS) effects. CNS effects can range from mild dizziness and lethargy to coma and convulsions. (12, 6)
TreatmentThere is no know antidote for chromium poisoning. Exposure is usually handled with symptomatic treatment. Methemoglobinemia can be treated with supplemental oxygen and methylene blue 1% solution administered intravenously slowly over five minutes followed by IV flush with normal saline. Methylene blue restores the iron in hemoglobin to its normal (reduced) oxygen-carrying state. (13, 6)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID119064
ChEMBL IDNot Available
ChemSpider IDNot Available
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDChromium(III) nitrate
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkChromium_nitrate
References
Synthesis ReferenceNot Available
MSDST3D1432.pdf
General References
  1. Salnikow K, Zhitkovich A: Genetic and epigenetic mechanisms in metal carcinogenesis and cocarcinogenesis: nickel, arsenic, and chromium. Chem Res Toxicol. 2008 Jan;21(1):28-44. Epub 2007 Oct 30. [17970581 ]
  2. Kim G, Yurkow EJ: Chromium induces a persistent activation of mitogen-activated protein kinases by a redox-sensitive mechanism in H4 rat hepatoma cells. Cancer Res. 1996 May 1;56(9):2045-51. [8616849 ]
  3. Schnekenburger M, Talaska G, Puga A: Chromium cross-links histone deacetylase 1-DNA methyltransferase 1 complexes to chromatin, inhibiting histone-remodeling marks critical for transcriptional activation. Mol Cell Biol. 2007 Oct;27(20):7089-101. Epub 2007 Aug 6. [17682057 ]
  4. Kimura T: [Molecular mechanism involved in chromium(VI) toxicity]. Yakugaku Zasshi. 2007 Dec;127(12):1957-65. [18057785 ]
  5. Keszler A, Piknova B, Schechter AN, Hogg N: The reaction between nitrite and oxyhemoglobin: a mechanistic study. J Biol Chem. 2008 Apr 11;283(15):9615-22. doi: 10.1074/jbc.M705630200. Epub 2008 Jan 17. [18203719 ]
  6. ATSDR - Agency for Toxic Substances and Disease Registry (2008). Toxicological profile for chromium. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  7. Wikipedia. Chromium. Last Updated 5 March 2009. [Link]
  8. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
  9. The Physical and Theoretical Chemistry Laboratory of Oxford University (2005). Material Safety Data Sheet (MSDS) for DDT. [Link]
  10. Wikipedia. Chromium(III) nitrate. Last Updated 29 May 2009. [Link]
  11. The Physical and Theoretical Chemistry Laboratory of Oxford University (2008). Material Safety Data Sheet (MSDS) for chromium (III) nitrate nonahydrate. [Link]
  12. ATSDR - Agency for Toxic Substances and Disease Registry (2007). Case Studies in Environmental Medicine. Nitrate/Nitrite Toxicity. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  13. Wikipedia. Methemoglobinemia. Last Updated 22 July 2009. [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated GenesNot Available

Targets

General Function:
Oxygen transporter activity
Specific Function:
Involved in oxygen transport from the lung to the various peripheral tissues.
Gene Name:
HBA1
Uniprot ID:
P69905
Molecular Weight:
15257.405 Da
References
  1. Keszler A, Piknova B, Schechter AN, Hogg N: The reaction between nitrite and oxyhemoglobin: a mechanistic study. J Biol Chem. 2008 Apr 11;283(15):9615-22. doi: 10.1074/jbc.M705630200. Epub 2008 Jan 17. [18203719 ]
  2. Wikipedia. Methemoglobinemia. Last Updated 22 July 2009. [Link]
General Function:
Oxygen transporter activity
Specific Function:
Involved in oxygen transport from the lung to the various peripheral tissues.LVV-hemorphin-7 potentiates the activity of bradykinin, causing a decrease in blood pressure.Spinorphin: functions as an endogenous inhibitor of enkephalin-degrading enzymes such as DPP3, and as a selective antagonist of the P2RX3 receptor which is involved in pain signaling, these properties implicate it as a regulator of pain and inflammation.
Gene Name:
HBB
Uniprot ID:
P68871
Molecular Weight:
15998.34 Da
References
  1. Keszler A, Piknova B, Schechter AN, Hogg N: The reaction between nitrite and oxyhemoglobin: a mechanistic study. J Biol Chem. 2008 Apr 11;283(15):9615-22. doi: 10.1074/jbc.M705630200. Epub 2008 Jan 17. [18203719 ]
  2. Wikipedia. Methemoglobinemia. Last Updated 22 July 2009. [Link]
General Function:
Oxygen transporter activity
Specific Function:
Involved in oxygen transport from the lung to the various peripheral tissues.
Gene Name:
HBD
Uniprot ID:
P02042
Molecular Weight:
16055.41 Da
References
  1. Keszler A, Piknova B, Schechter AN, Hogg N: The reaction between nitrite and oxyhemoglobin: a mechanistic study. J Biol Chem. 2008 Apr 11;283(15):9615-22. doi: 10.1074/jbc.M705630200. Epub 2008 Jan 17. [18203719 ]
  2. Wikipedia. Methemoglobinemia. Last Updated 22 July 2009. [Link]
General Function:
Oxygen transporter activity
Specific Function:
The epsilon chain is a beta-type chain of early mammalian embryonic hemoglobin.
Gene Name:
HBE1
Uniprot ID:
P02100
Molecular Weight:
16202.71 Da
References
  1. Keszler A, Piknova B, Schechter AN, Hogg N: The reaction between nitrite and oxyhemoglobin: a mechanistic study. J Biol Chem. 2008 Apr 11;283(15):9615-22. doi: 10.1074/jbc.M705630200. Epub 2008 Jan 17. [18203719 ]
  2. Wikipedia. Methemoglobinemia. Last Updated 22 July 2009. [Link]
General Function:
Oxygen transporter activity
Specific Function:
Gamma chains make up the fetal hemoglobin F, in combination with alpha chains.
Gene Name:
HBG1
Uniprot ID:
P69891
Molecular Weight:
16140.37 Da
References
  1. Keszler A, Piknova B, Schechter AN, Hogg N: The reaction between nitrite and oxyhemoglobin: a mechanistic study. J Biol Chem. 2008 Apr 11;283(15):9615-22. doi: 10.1074/jbc.M705630200. Epub 2008 Jan 17. [18203719 ]
  2. Wikipedia. Methemoglobinemia. Last Updated 22 July 2009. [Link]
General Function:
Gamma chains make up the fetal hemoglobin F, in combination with alpha chains.
Specific Function:
Heme binding
Gene Name:
HBG2
Uniprot ID:
P69892
Molecular Weight:
16126.35 Da
References
  1. Keszler A, Piknova B, Schechter AN, Hogg N: The reaction between nitrite and oxyhemoglobin: a mechanistic study. J Biol Chem. 2008 Apr 11;283(15):9615-22. doi: 10.1074/jbc.M705630200. Epub 2008 Jan 17. [18203719 ]
  2. Wikipedia. Methemoglobinemia. Last Updated 22 July 2009. [Link]
General Function:
Oxygen transporter activity
Specific Function:
Not Available
Gene Name:
HBM
Uniprot ID:
Q6B0K9
Molecular Weight:
15617.97 Da
References
  1. Keszler A, Piknova B, Schechter AN, Hogg N: The reaction between nitrite and oxyhemoglobin: a mechanistic study. J Biol Chem. 2008 Apr 11;283(15):9615-22. doi: 10.1074/jbc.M705630200. Epub 2008 Jan 17. [18203719 ]
  2. Wikipedia. Methemoglobinemia. Last Updated 22 July 2009. [Link]
General Function:
Oxygen transporter activity
Specific Function:
Not Available
Gene Name:
HBQ1
Uniprot ID:
P09105
Molecular Weight:
15507.575 Da
References
  1. Keszler A, Piknova B, Schechter AN, Hogg N: The reaction between nitrite and oxyhemoglobin: a mechanistic study. J Biol Chem. 2008 Apr 11;283(15):9615-22. doi: 10.1074/jbc.M705630200. Epub 2008 Jan 17. [18203719 ]
  2. Wikipedia. Methemoglobinemia. Last Updated 22 July 2009. [Link]
General Function:
Oxygen transporter activity
Specific Function:
The zeta chain is an alpha-type chain of mammalian embryonic hemoglobin.
Gene Name:
HBZ
Uniprot ID:
P02008
Molecular Weight:
15636.845 Da
References
  1. Keszler A, Piknova B, Schechter AN, Hogg N: The reaction between nitrite and oxyhemoglobin: a mechanistic study. J Biol Chem. 2008 Apr 11;283(15):9615-22. doi: 10.1074/jbc.M705630200. Epub 2008 Jan 17. [18203719 ]
  2. Wikipedia. Methemoglobinemia. Last Updated 22 July 2009. [Link]
10. DNA
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2008). Toxicological profile for chromium. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Transcription regulatory region sequence-specific dna binding
Specific Function:
Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Deacetylates SP proteins, SP1 and SP3, and regulates their function. Component of the BRG1-RB1-HDAC1 complex, which negatively regulates the CREST-mediated transcription in resting neurons. Upon calcium stimulation, HDAC1 is released from the complex and CREBBP is recruited, which facilitates transcriptional activation. Deacetylates TSHZ3 and regulates its transcriptional repressor activity. Deacetylates 'Lys-310' in RELA and thereby inhibits the transcriptional activity of NF-kappa-B. Deacetylates NR1D2 and abrogates the effect of KAT5-mediated relieving of NR1D2 transcription repression activity. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. Involved in CIART-mediated transcriptional repression of the circadian transcriptional activator: CLOCK-ARNTL/BMAL1 heterodimer. Required for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER complex or CRY1 through histone deacetylation.
Gene Name:
HDAC1
Uniprot ID:
Q13547
Molecular Weight:
55102.615 Da
References
  1. Schnekenburger M, Talaska G, Puga A: Chromium cross-links histone deacetylase 1-DNA methyltransferase 1 complexes to chromatin, inhibiting histone-remodeling marks critical for transcriptional activation. Mol Cell Biol. 2007 Oct;27(20):7089-101. Epub 2007 Aug 6. [17682057 ]
General Function:
Transcriptional activator activity, rna polymerase ii core promoter proximal region sequence-specific binding
Specific Function:
Activates the metallothionein I promoter. Binds to the metal responsive element (MRE).
Gene Name:
MTF1
Uniprot ID:
Q14872
Molecular Weight:
80956.22 Da
References
  1. Kimura T: [Molecular mechanism involved in chromium(VI) toxicity]. Yakugaku Zasshi. 2007 Dec;127(12):1957-65. [18057785 ]
General Function:
Rna polymerase ii carboxy-terminal domain kinase activity
Specific Function:
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. Mediates phosphorylation of TPR in respons to EGF stimulation. May play a role in the spindle assembly checkpoint. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation.Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity.
Gene Name:
MAPK1
Uniprot ID:
P28482
Molecular Weight:
41389.265 Da
References
  1. Kim G, Yurkow EJ: Chromium induces a persistent activation of mitogen-activated protein kinases by a redox-sensitive mechanism in H4 rat hepatoma cells. Cancer Res. 1996 May 1;56(9):2045-51. [8616849 ]
General Function:
Phosphatase binding
Specific Function:
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade.
Gene Name:
MAPK3
Uniprot ID:
P27361
Molecular Weight:
43135.16 Da
References
  1. Kim G, Yurkow EJ: Chromium induces a persistent activation of mitogen-activated protein kinases by a redox-sensitive mechanism in H4 rat hepatoma cells. Cancer Res. 1996 May 1;56(9):2045-51. [8616849 ]