Disease relevance of Cr(VI)

• Selection for Cr(VI) resistant, MMR-deficient cells may explain the very high frequency of lung cancers with microsatellite instability among chromate workers [1].
• The lung and kidney may be more sensitive than liver to chromium-induced DNA damage, an observation which correlates with the reported toxicity and carcinogenicity data for chromium(VI) in both animals and humans [2].
• Chromium in the form of Cr(III) as well as Cr(VI) diminished the fidelity by which Escherichia coli DNA polymerase I copies polynucleotide templates [3].
• Incubation of rat liver cytosolic or microsomal fractions with chromium(VI) led to a dramatic decrease in chromium(VI) mutagenicity, as determined by the Ames Salmonella assay using the TA100 tester strain [4].
• These results confirm the view that the active mutagenic agent in intact cell systems is Cr(VI), but indicate that industrial Cr(III) compounds cannot be considered genetically inert, as they can be contaminated by Cr(VI) and induce chromosomal aberrations [5].

Psychiatry related information on Cr(VI)

• Hence, lung cancer can only be induced when chromium(VI) doses overwhelm these defense mechanisms [6].
• Aqueous Cr(VI) removal rate half-lives varied from 1.2 to 230 h with the fastest at the highest base concentration, lowest Al concentration, greatest reaction time, and lowest Cr(VI) concentration in the leaching solution [7].
• The effects caused by Cr(VI) on the motor activity in rats could be an indication of the neurotoxicity of this metal [8].

High impact information on Cr(VI)

• These results suggest that glutathione enhances chromium(VI)-induced DNA damage through metabolic activation of chromium(VI) [9].
• The role of glutathione and cytochrome P-450 in the production of DNA damage by chromium(VI) was examined in chicken embryo hepatocytes by the alkaline elution technique [9].
• The in vitro base damage pattern generated by Cr(VI), ascorbate, and H2O2 was similar to that of the other metal ions, with the exception of several unique positions; these were heavily damaged only in the presence of Cr(VI) [10].
• Chromium(VI)- and chromium(III)-induced AI was a stable phenotype [11].
• We previously showed that carcinogenic nickel, arsenic, and chromium(VI) compounds induced anchorage independence (AI) in diploid human fibroblastic cells (HFC) derived from foreskins (K [11].

Chemical compound and disease context of Cr(VI)

• Specifically, at a 0.50 LD(50) dose, naphthalene and Cr(VI) induced the greatest toxicity in the liver tissue of mice, and naphthalene and endrin exhibited the greatest effect in the brain tissue [12].
• Since the hydroxyl radicals have been suggested to play an important role in Cr(VI) toxicity, this study provides a basis for a recent observation that Cr(VI) mutagenesis is strongly oxygen dependent [13].
• In a defined coculture of a Cr(VI) reducer, Escherichia coli ATCC 33456, and a phenol degrader, Pseudomonas putida DMP-1, simultaneous reduction of Cr(VI) and degradation of phenol was observed [14].
• An NAD(P)H-dependent Cr(VI) reductase (molecular weight = 65,000) was purified from a Cr(VI)-resistant bacterium, Pseudomonas ambigua G-1 [15].
• Results showed that although Cr(VI) was completely reduced by the three consortia, Cr(VI) inhibited cell growth, with sulfate-reducing bacteria being particularly sensitive to Cr(VI) toxicity relative to other bacteria in the consortia [16].

Biological context of Cr(VI)

• Treatment of human lung epithelial cells (A549) with Cr(VI) caused apoptosis as measured by DNA fragmentation, mitochondria damage, and cell morphology [17].
• Chromium(VI) treatment of these NF-kappaB-inhibited cells induced necrotic-like cell death [18].
• However, the effects of Cr(VI) on signal transduction leading to gene expression are not resolved [19].
• Chromium(VI) down-regulates heavy metal-induced metallothionein gene transcription by modifying transactivation potential of the key transcription factor, metal-responsive transcription factor 1 [20].
• Chromium(VI) compounds are amongst the most widely encountered industrial carcinogens and are of increasing concern with respect to environmental exposure [21].

Anatomical context of Cr(VI)

• Of three enzyme inducers injected i.p. which modified the spectral properties and/or concentration of cytochromes P-450 in liver and lung microsomes, only Aroclor 1254 proved to stimulate chromium(VI) metabolism in lung cells [22].
• In the lung cytosol, a slight yet significant stimulation of some of these enzyme activities was determined by the daily intratracheal instillations of high doses of chromium(VI) itself for 4 weeks, a condition which has been found to enhance the pulmonary metabolism of this metal ion [23].
• Specificity and inducibility of the metabolic reduction of chromium(VI) mutagenicity by subcellular fractions of rat tissues [22].
• Chromium(VI) salts are well known to be mutagens and carcinogens and to easily cross the cell membranes [24].
• NER deficiency created by the loss of XPA in fibroblasts or by knockdown of this protein by stable expression of small interfering RNA in H460 cells increased apoptosis and clonogenic death by Cr(VI), providing genetic evidence for the role of monofunctional chromium-DNA adducts in the toxic effects of this metal [25].

Associations of Cr(VI) with other chemical compounds

• A much smaller proportion of the chromium bound to chromatin was associated with the DNA after treatment with chromium(III) than after treatment with chromium(VI) [26].
• Similarly, cytosolic reduction of chromium(VI) was partially inhibited by selective metabolic depletors of both coenzymes of DT-diaphorase, i.e., NADPH and NADH [23].
• In liver cells, Aroclor 1254 and to a lower extent phenobarbital induced chromium(VI) reduction, while 3-methylcholanthrene was ineffective [22].
• Inhibition of NO production by the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide and by NO synthase inhibitor aminoguanidine effectively inhibited S-nitrosylation of Bcl-2, increased its ubiquitination, and promoted apoptotic cell death induced by chromium (VI) [27].
• A comparative study of calf thymus DNA binding to Cr(III) and Cr(VI) ions. Evidence for the guanine N-7-chromium-phosphate chelate formation [24].

Gene context of Cr(VI)

• p38 Signaling-mediated hypoxia-inducible factor 1alpha and vascular endothelial growth factor induction by Cr(VI) in DU145 human prostate carcinoma cells [28].
• Chromium (VI) activates ataxia telangiectasia mutated (ATM) protein. Requirement of ATM for both apoptosis and recovery from terminal growth arrest [29].
• Oppositely, activation of ERK, JNK and p38 by Cr(VI) does not affect cytotoxicity [30].
• The activated p38 decreased markedly and rapidly and the activated JNK decreased gradually when Cr(VI) was removed from media [30].
• These results, taken together with the recombinogenic effects of Cr(VI) in yeast containing a functional RAD52 gene, suggest that RAD52-mediated recombination is critical for the normal processing of lethal Cr-induced genetic lesions and exit from G(2) arrest [31].

Analytical, diagnostic and therapeutic context of Cr(VI)

• Cr(VI)-induced apoptosis is contributed to ROS generation, resulting from cellular reduction of Cr(VI) as measured by flow cytometric analysis of the stained cells, oxygen consumption, and electron spin resonance spin trapping [17].
• Chromium(VI) compounds--Ca, Sr, Zn and Pb chromates--were studied for cytotoxicity and morphological transformation in Syrian hamster embryo (SHE) cells in relation to their solubilization in cell culture conditions and intracellular Cr concentration [32].
• This sorbent was found to be stable, cost-effective, efficient for preconcentration of Cr(VI) present in the aqueous samples, and amenable to direct quantitative analysis of Cr(VI) held in it by neutron activation analysis and spectrophotometry [33].
• Speciation of chromium (III) and chromium (VI) by capillary electrophoresis with contactless conductometric detection and dual opposite end injection [34].
• Both the rate and extent of Cr(VI) reduction and phenol degradation were significantly influenced by the population composition of the coculture [14].

References