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1000 Titel
  • Synthesis and in vitro characterization of the genotoxic, mutagenic and cell-transforming potential of nitrosylated heme
1000 Autor/in
  1. Kostka, Tina |
  2. Fohrer, Jörg |
  3. Guigas, Claudia |
  4. Briviba, Karlis |
  5. Seiwert, Nina |
  6. Fahrer, Jörg |
  7. Steinberg, Pablo |
  8. Empl, Michael T. |
1000 Erscheinungsjahr 2020
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2020-07-15
1000 Erschienen in
1000 Quellenangabe
  • 94(11):3911-3927
1000 Copyrightjahr
  • 2020
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1007/s00204-020-02846-8 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603461/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Data from epidemiological studies suggest that consumption of red and processed meat is a factor contributing to colorectal carcinogenesis. Red meat contains high amounts of heme, which in turn can be converted to its nitrosylated form, NO-heme, when adding nitrite-containing curing salt to meat. NO-heme might contribute to colorectal cancer formation by causing gene mutations and could thereby be responsible for the association of (processed) red meat consumption with intestinal cancer. Up to now, neither in vitro nor in vivo studies characterizing the mutagenic and cell transforming potential of NO-heme have been published due to the fact that the pure compound is not readily available. Therefore, in the present study, an already existing synthesis protocol was modified to yield, for the first time, purified NO-heme. Thereafter, newly synthesized NO-heme was chemically characterized and used in various in vitro approaches at dietary concentrations to determine whether it can lead to DNA damage and malignant cell transformation. While NO-heme led to a significant dose-dependent increase in the number of DNA strand breaks in the comet assay and was mutagenic in the HPRT assay, this compound tested negative in the Ames test and failed to induce malignant cell transformation in the BALB/c 3T3 cell transformation assay. Interestingly, the non-nitrosylated heme control showed similar effects, but was additionally able to induce malignant transformation in BALB/c 3T3 murine fibroblasts. Taken together, these results suggest that it is the heme molecule rather than the NO moiety which is involved in driving red meat-associated carcinogenesis.
1000 Sacherschließung
lokal Nitrosylated heme
lokal BALB 3T3 Cells [MeSH]
lokal Nitric Oxide/toxicity [MeSH]
lokal Cell Line [MeSH]
lokal Heme/chemistry [MeSH]
lokal Genotoxicity and Carcinogenicity
lokal Risk Factors [MeSH]
lokal DNA Damage/drug effects [MeSH]
lokal Single-Cell Analysis [MeSH]
lokal Red Meat/toxicity [MeSH]
lokal Caco-2 Cells [MeSH]
lokal Colon cancer
lokal Carcinogenesis/chemically induced [MeSH]
lokal Mutagenicity
lokal Cricetinae [MeSH]
lokal Intestinal Neoplasms/chemically induced [MeSH]
lokal Comet Assay [MeSH]
lokal Mutation [MeSH]
lokal Genotoxicity
lokal Humans [MeSH]
lokal Animals [MeSH]
lokal Nitric Oxide/chemistry [MeSH]
lokal Cell Transformation, Neoplastic/drug effects [MeSH]
lokal Processed red meat
lokal Mice [MeSH]
lokal Heme/toxicity [MeSH]
lokal Mutagenesis [MeSH]
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0001-8212-694X|https://frl.publisso.de/adhoc/uri/Rm9ocmVyLCBKw7ZyZw==|https://frl.publisso.de/adhoc/uri/R3VpZ2FzLCBDbGF1ZGlh|https://frl.publisso.de/adhoc/uri/QnJpdmliYSwgS2FybGlz|https://frl.publisso.de/adhoc/uri/U2Vpd2VydCwgTmluYQ==|https://frl.publisso.de/adhoc/uri/RmFocmVyLCBKw7ZyZw==|https://frl.publisso.de/adhoc/uri/U3RlaW5iZXJnLCBQYWJsbw==|https://frl.publisso.de/adhoc/uri/RW1wbCwgTWljaGFlbCBULg==
1000 Hinweis
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1000 @id frl:6466340.rdf
1000 Erstellt am 2023-11-16T22:15:14.520+0100
1000 Erstellt von 322
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1000 Zuletzt bearbeitet 2023-12-01T04:04:42.895+0100
1000 Objekt bearb. Fri Dec 01 04:04:42 CET 2023
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