Details
| Original language | English |
|---|---|
| Pages (from-to) | 3911-3927 |
| Number of pages | 17 |
| Journal | Archives of toxicology |
| Volume | 94 |
| Issue number | 11 |
| Early online date | 15 Jul 2020 |
| Publication status | Published - Nov 2020 |
Abstract
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.
Keywords
- Colon cancer, Genotoxicity, Mutagenicity, Nitrosylated heme, Processed red meat
ASJC Scopus subject areas
- Pharmacology, Toxicology and Pharmaceutics(all)
- Toxicology
- Environmental Science(all)
- Health, Toxicology and Mutagenesis
Sustainable Development Goals
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In: Archives of toxicology, Vol. 94, No. 11, 11.2020, p. 3911-3927.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Synthesis and in vitro characterization of the genotoxic, mutagenic and cell-transforming potential of nitrosylated heme
AU - Kostka, Tina
AU - Fohrer, Jörg
AU - Guigas, Claudia
AU - Briviba, Karlis
AU - Seiwert, Nina
AU - Fahrer, Jörg
AU - Steinberg, Pablo
AU - Empl, Michael T.
N1 - Funding information: The study was partly supported by the German Research Foundation (DFG; Grant no. STE 493/21-1 and FA 1034/3-3). Acknowledgements
PY - 2020/11
Y1 - 2020/11
N2 - 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.
AB - 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.
KW - Colon cancer
KW - Genotoxicity
KW - Mutagenicity
KW - Nitrosylated heme
KW - Processed red meat
UR - http://www.scopus.com/inward/record.url?scp=85087989386&partnerID=8YFLogxK
U2 - 10.1007/s00204-020-02846-8
DO - 10.1007/s00204-020-02846-8
M3 - Article
C2 - 32671443
AN - SCOPUS:85087989386
VL - 94
SP - 3911
EP - 3927
JO - Archives of toxicology
JF - Archives of toxicology
SN - 0340-5761
IS - 11
ER -