Combined genotoxic effects of a polycyclic aromatic hydrocarbon (B(a)P) and an heterocyclic amine (PhIP) in relation to colorectal carcinogenesis.

Colorectal neoplasia is the third most common cancer worldwide. Environmental factors such as diet are known to be involved in the etiology of this cancer. Several epidemiological studies have suggested that specific neo-formed mutagenic compounds related to meat consumption are an underlying factor...

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Autores principales:	Emilien L Jamin, Anne Riu, Thierry Douki, Laurent Debrauwer, Jean-Pierre Cravedi, Daniel Zalko, Marc Audebert
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/39771d298f9e4fc98816af087586c468
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spelling	oai:doaj.org-article:39771d298f9e4fc98816af087586c4682021-11-18T07:54:31ZCombined genotoxic effects of a polycyclic aromatic hydrocarbon (B(a)P) and an heterocyclic amine (PhIP) in relation to colorectal carcinogenesis.1932-620310.1371/journal.pone.0058591https://doaj.org/article/39771d298f9e4fc98816af087586c4682013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23484039/?tool=EBIhttps://doaj.org/toc/1932-6203Colorectal neoplasia is the third most common cancer worldwide. Environmental factors such as diet are known to be involved in the etiology of this cancer. Several epidemiological studies have suggested that specific neo-formed mutagenic compounds related to meat consumption are an underlying factor involved in the association between diet and colorectal cancer. Heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) are known mutagens and possible human carcinogens formed at the same time in meat during cooking processes. We studied the genotoxicity of the model PAH benzo(a)pyrene (B(a)P) and HCA 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), alone or in mixture, using the mouse intestinal cell line Apc(Min/+), mimicking the early step of colorectal carcinogenesis, and control Apc(+/+) cells. The genotoxicity of B(a)P and PhIP was investigated using both cell lines, through the quantification of B(a)P and PhIP derived DNA adducts, as well as the use of a genotoxic assay based on histone H2AX phosphorylation quantification. Our results demonstrate that heterozygous Apc mutated cells are more effective to metabolize B(a)P. We also established in different experiments that PhIP and B(a)P were more genotoxic on Apc (Min/+) cells compared to Apc (+/+) . Moreover when tested in mixture, we observed a combined genotoxicity of B(a)P and PhIP on the two cell lines, with an increase of PhIP derived DNA adducts in the presence of B(a)P. Because of their genotoxic effects observed on heterozygous Apc mutated cells and their possible combined genotoxic effects, both B(a)P and PhIP, taken together, could be implicated in the observed association between meat consumption and colorectal cancer.Emilien L JaminAnne RiuThierry DoukiLaurent DebrauwerJean-Pierre CravediDaniel ZalkoMarc AudebertPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e58591 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Emilien L Jamin Anne Riu Thierry Douki Laurent Debrauwer Jean-Pierre Cravedi Daniel Zalko Marc Audebert Combined genotoxic effects of a polycyclic aromatic hydrocarbon (B(a)P) and an heterocyclic amine (PhIP) in relation to colorectal carcinogenesis.
description	Colorectal neoplasia is the third most common cancer worldwide. Environmental factors such as diet are known to be involved in the etiology of this cancer. Several epidemiological studies have suggested that specific neo-formed mutagenic compounds related to meat consumption are an underlying factor involved in the association between diet and colorectal cancer. Heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) are known mutagens and possible human carcinogens formed at the same time in meat during cooking processes. We studied the genotoxicity of the model PAH benzo(a)pyrene (B(a)P) and HCA 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), alone or in mixture, using the mouse intestinal cell line Apc(Min/+), mimicking the early step of colorectal carcinogenesis, and control Apc(+/+) cells. The genotoxicity of B(a)P and PhIP was investigated using both cell lines, through the quantification of B(a)P and PhIP derived DNA adducts, as well as the use of a genotoxic assay based on histone H2AX phosphorylation quantification. Our results demonstrate that heterozygous Apc mutated cells are more effective to metabolize B(a)P. We also established in different experiments that PhIP and B(a)P were more genotoxic on Apc (Min/+) cells compared to Apc (+/+) . Moreover when tested in mixture, we observed a combined genotoxicity of B(a)P and PhIP on the two cell lines, with an increase of PhIP derived DNA adducts in the presence of B(a)P. Because of their genotoxic effects observed on heterozygous Apc mutated cells and their possible combined genotoxic effects, both B(a)P and PhIP, taken together, could be implicated in the observed association between meat consumption and colorectal cancer.
format	article
author	Emilien L Jamin Anne Riu Thierry Douki Laurent Debrauwer Jean-Pierre Cravedi Daniel Zalko Marc Audebert
author_facet	Emilien L Jamin Anne Riu Thierry Douki Laurent Debrauwer Jean-Pierre Cravedi Daniel Zalko Marc Audebert
author_sort	Emilien L Jamin
title	Combined genotoxic effects of a polycyclic aromatic hydrocarbon (B(a)P) and an heterocyclic amine (PhIP) in relation to colorectal carcinogenesis.
title_short	Combined genotoxic effects of a polycyclic aromatic hydrocarbon (B(a)P) and an heterocyclic amine (PhIP) in relation to colorectal carcinogenesis.
title_full	Combined genotoxic effects of a polycyclic aromatic hydrocarbon (B(a)P) and an heterocyclic amine (PhIP) in relation to colorectal carcinogenesis.
title_fullStr	Combined genotoxic effects of a polycyclic aromatic hydrocarbon (B(a)P) and an heterocyclic amine (PhIP) in relation to colorectal carcinogenesis.
title_full_unstemmed	Combined genotoxic effects of a polycyclic aromatic hydrocarbon (B(a)P) and an heterocyclic amine (PhIP) in relation to colorectal carcinogenesis.
title_sort	combined genotoxic effects of a polycyclic aromatic hydrocarbon (b(a)p) and an heterocyclic amine (phip) in relation to colorectal carcinogenesis.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/39771d298f9e4fc98816af087586c468
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Combined genotoxic effects of a polycyclic aromatic hydrocarbon (B(a)P) and an heterocyclic amine (PhIP) in relation to colorectal carcinogenesis.

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