Toxicities of aflatoxins and precursors on HepG2 and Caco-2 cells

THEUMER, MG; BORIN, C; PUEL, O; OSWALD, I

Rotterdam

Congreso; 7th Conference of The World Mycotoxin Forum, XIIIth IUPAC International Symposium on Mycotoxins and Phycotoxins; 2012

IUPAC

Aflatoxin B1 (AFB1), mainly produced by Aspergillus flavus and A. parasiticus, is frequently found as contaminant of cereals and by-products, causing a wide range of toxic effects. It is a genotoxic mycotoxin that leads to mutations and cancer in humans and animals. Strategies to limit the exposure include agricultural practices management, and the use of pesticides or microorganisms that might block the AFB1 biosynthesis. Nevertheless, the accumulation of aflatoxin intermediates, or even of other metabolic pathway products such as the cyclopiazonic acid, may be also toxic for consumers. This work was aimed to estimate the hepatic and intestinal cytotoxicities of the aflatoxins: AFB1, AFG1, AFB2, AFG2; the early metabolic precursor averantin (AVN); the late biosynthetic intermediaries sterigmatocystin (SC) and o-methylsterigmatocystin (OMSC); and the cyclopiazonic acid (CPA). The human intestinal Caco-2 and hepatic HepG2 cell lines were incubated with the toxins for 48 and 72 hours, and then the decrease in the ATP level was used as marker of cytotoxicity. The toxicity of AFB1 was studied in the range 0-30 μM. Besides, three levels of exposure (0.3, 3 and 30 μM) were tested to assess comparatively the mycotoxin toxicities. Whilst the HepG2 cells were more sensible to AFB1 than the Caco-2 cells, the inverse was observed with OMSC and AFG1. In general, the Caco-2 and HepG2 cell susceptibilities to mycotoxins were in the following order, respectively: SC ≈ OMSC > AFG1 > AVN ≈ CPA > AFB2 ≈ AFG2, and SC > OMSC ≈ AFG1 ≈ AVN ≈ CPA > AFB2 ≈ AFG2. The results of this study show that the metabolic precursors of aflatoxins and the CPA might have the same or even higher toxicity than AFB1 to intestinal and hepatic cells. This should be taking into account for the development of new strategies intended to reduce the aflatoxins intake.