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METAQUANT metagenomics platform. © INRA, BEAUCARDET William

Cocktail effects of toxic substances demonstrated in vitro

“Barbecue” cocktail effect

A specific synergistic effect between two types of compounds produced when grilling meat was demonstrated for the first time on mouse cell lines. One of the compounds increases the carcinogenic potential of the other by promoting its metabolization in a genotoxic manner. This synergy could explain in part the link observed between the presence of these compounds in food and colon cancer.

By Pascale Mollier, translated by Teri Jones-Villeneuve
Updated on 11/22/2016
Published on 06/27/2013

Heating meat to high temperatures produces several types of potentially carcinogenic compounds. They are a possible factor in colon cancer, the third most frequent cancer in the world. Two types of compounds, heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs), are of particular concern.

The cocktail effect revealed

Scientists from the ToxAlim unit demonstrated very recently that there is a synergistic effect between two compounds that are representative of each of these classes: an HCA-type compound, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and a PAH-type compound, benzo(a)pyrene (B(a)P). More precisely, B(a)P causes a genotoxic metabolite (1) from PhIP to form.

The cell model used in this study is closer to a real-world situation than in previous studies. In prior studies, researchers used cancerous cells. But in the process of cancer development, which occurs in several stages, carcinogenic substances primarily target healthy or precancerous cells. Precancerous cells undergo a mutation in a particular gene (the adenomatous polyposis coli (APC) gene), causing them to be even more sensitive to carcinogenic substances than healthy cells. In this study, the synergistic effects of B(a)P and PhIP were shown on two types of mouse intestinal cells, healthy and precancerous (mutated by the APC gene).

The synergistic effects between compounds produced simultaneously when cooking meat at high temperatures are one way to explain the correlations observed between consuming cooked meat and colorectal cancer.

(1) The genotoxic effect is measured using the test developed by the team. This test makes it possible to quantify breaks in DNA via a biomarker: a histone that is phosphorylated when the DNA is damaged (see the study introduction page).

Contact(s)
Scientific contact(s):

Associated Division(s):
Nutrition, Chemical Food Safety and Consumer Behaviour, Animal Health
Associated Centre(s):
Occitanie-Toulouse

Reference

Jamin E.L., Riu A., Douki T., Debrauwer L., Cravedi J-P, Zalko D. and Audebert M. 2013. Combined Genotoxic Effects of a Polycyclic Aromatic Hydrocarbon (B(a)P) and an Heterocyclic Amine (PhIP) in Relation to Colorectal Carcinogenesis. Plos One 8, Issue 3, e58491