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Time-series analysis of gene expression profiles induced by nitrosamides and nitrosamines elucidates modes of action underlying their genotoxicity in human colon cells

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National Hellenic Research Foundation (NHRF)   

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Time-series analysis of gene expression profiles induced by nitrosamides and nitrosamines elucidates modes of action underlying their genotoxicity in human colon cells
van Herwijnen, Marcel H. M.
Kleinjans, Jos C. S.
de Kok, Theo M. C. M.
Brauers, Karen J. J.
Hebels, Dennie G. A. J.
Γεωργιάδης, Παναγιώτης
Κυρτόπουλος, Σωτήριος Α.
Άρθρο σε επιστημονικό περιοδικό
2011-12-15
CLARE
N-nitroso compounds (NOCs) may represent a carcinogenic risk to humans following endogenous colonic nitrosation processes. We used the colon adenocarcinoma cell line Caco-2 to investigate transcriptomic changes at three time points (1, 6, 24 h) following exposure to genotoxic concentrations of six different NOCs (two nitrosamides, four nitrosamines) with the purpose of identifying biological processes that may play a part in the carcinogenicity of these compounds. This is especially important for nitrosamide exposure where, in light of their high reactivity, important gene expression modifications may take place early in the exposure. We also analyzed NOC-induced O(6)-methylguanine adducts in relation to transcriptomics since these adducts may influence the expression of genes pivotal in NOC-associated carcinogenicity. Many modified pathways appeared related to DNA damage, cell cycle, apoptosis, growth factor signaling and differentiation, which are linked with carcinogenicity. Nitrosamides showed the strongest response at 1 h of exposure, while nitrosamines had the strongest effect at 6 and 24 h. Additionally, methylation was strongly associated with processes that may contribute to the carcinogenic risk. In summary, we have found that NOC-induced gene expression changes vary over time and that many of the modified pathways and processes indicate a carcinogenic risk associated with NOC exposure.
Τοξικολογία (EL)
Toxicology. Poisons (EN)
O(6)-methylguanine
Alkylating agents
Time-series
N-nitroso compounds
Colon carcinogenesis
Toxicogenomics
Αγγλική γλώσσα
Elsevier Ireland Limited
Toxicology Letters
https://rightsstatements.org/page/InC/1.0/?language=en
© 2011 Elsevier Ireland Ltd. All rights reserved.
© 2011 Elsevier Ireland Ltd. All rights reserved. (EN)
National Hellenic Research Foundation (NHRF)
Helios - Repository of the National Hellenic Research Foundation (NHRF)
Ινστιτούτο Χημικής Βιολογίας (ΙΧΒ/ΕΙΕ)
νστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο



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