{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T14:36:02Z","timestamp":1786631762134,"version":"build-2736575974"},"reference-count":133,"publisher":"American Chemical Society (ACS)","issue":"5","license":[{"start":{"date-parts":[[2017,12,29]],"date-time":"2017-12-29T00:00:00Z","timestamp":1514505600000},"content-version":"vor","delay-in-days":4705,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Nickel compounds are known to cause respiratory cancer in humans and induce tumors in experimental animals. The underlying molecular mechanisms may involve genotoxic effects; however, the data from different research groups are not easy to reconcile. Here, we challenge the common premise that direct genotoxic effects are central to nickel carcinogenesis and probably to that of other metals. Instead, we propose that it is formation of metal complexes with proteins and other molecules that changes cellular homeostasis and provides conditions for selection of cells with transformed phenotype. This is concordant with the major requirement for nickel carcinogenicity, which is prolonged action on the target tissue. If DNA is not the main nickel target, is there another unique molecule that can be attacked with carcinogenic consequences? Our recent observations indicate that ascorbate may be such a molecule. Nickel depletes intracellular ascorbate, which leads to the inhibition of cellular hydroxylases, manifested by the loss of hypoxia-inducible factor (HIF)-1\u03b1 and - 2\u03b1 hydroxylation and hypoxia-like stress. Proline hydroxylation is crucial for collagen and extracellular matrix assembly as well as for assembly of other protein molecules that have collagen-like domains, including surfactants and complement. Thus, the depletion of ascorbate by chronic exposure to nickel could be deleterious for lung cells and may lead to lung cancer.<\/jats:p>","DOI":"10.1289\/ehp.7605","type":"journal-article","created":{"date-parts":[[2005,2,10]],"date-time":"2005-02-10T14:10:50Z","timestamp":1108044650000},"page":"577-584","source":"Crossref","is-referenced-by-count":50,"title":["Ascorbate Depletion: A Critical Step in Nickel Carcinogenesis?"],"prefix":"10.1021","volume":"113","author":[{"given":"Konstantin","family":"Salnikow","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazimierz S.","family":"Kasprzak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2005,2,10]]},"reference":[{"key":"2026080607030126800_micit1","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1093\/jn\/134.3.501","article-title":"Duodenal ascorbate levels are changed in mice with altered iron metabolism","volume":"134","author":"Atanasova","year":"2004","journal-title":"J Nutr"},{"key":"2026080607030126800_micit2","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/S0162-0134(99)00169-5","article-title":"Molecular models in nickel carcinogenesis","volume":"79","author":"Bal","year":"2000","journal-title":"J Inorg Biochem"},{"key":"2026080607030126800_micit3","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/0076-6879(90)88013-Z","article-title":"Phthalate dioxygenase","volume":"188","author":"Batie","year":"1990","journal-title":"Methods Enzymol"},{"key":"2026080607030126800_micit4","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1016\/S0021-9258(19)75664-6","article-title":"Purification and characterization of phthalate oxygenase and phthalate oxygenase reductase from Pseudomonas cepacia","volume":"262","author":"Batie","year":"1987","journal-title":"J Biol Chem"},{"key":"2026080607030126800_micit5","first-page":"1041","article-title":"Differences in anchorage-dependent growth and tumorigenicities between transformed C3H\/10T 1\/2 cells with morphologies that are or are not reverted to a normal phenotype by ascorbic acid","volume":"42","author":"Benedict","year":"1982","journal-title":"Cancer Res"},{"key":"2026080607030126800_micit6","first-page":"3815","article-title":"Induction of anchorage independence in human diploid foreskin fibroblasts by carcinogenic metal salts","volume":"47","author":"Biedermann","year":"1987","journal-title":"Cancer Res"},{"key":"2026080607030126800_micit7","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/0165-7992(86)90056-4","article-title":"Assessment of the uptake and mutagenicity of nickel chloride in salmonella tester strains","volume":"175","author":"Biggart","year":"1986","journal-title":"Mutat Res"},{"key":"2026080607030126800_micit8","first-page":"41","article-title":"Molecular orbital study of coordinated dioxygen. 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