Aflatoxin B1 and M1: Biological Properties and Their Involvement in Cancer Development.

Silvia Marchese,Salvatore Velotto,Lorella Severino,Andrea Ariano,Susan Costantini,Andrea Polo

doi:10.3390/toxins10060214

Silvia Marchese, Salvatore Velotto + Show 4 more

Open Access

https://doi.org/10.3390/toxins10060214

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Abstract

Aflatoxins are fungal metabolites found in feeds and foods. When the ruminants eat feedstuffs containing Aflatoxin B1 (AFB1), this toxin is metabolized and Aflatoxin M1 (AFM1) is excreted in milk. International Agency for Research on Cancer (IARC) classified AFB1 and AFM1 as human carcinogens belonging to Group 1 and Group 2B, respectively, with the formation of DNA adducts. In the last years, some epidemiological studies were conducted on cancer patients aimed to evaluate the effects of AFB1 and AFM1 exposure on cancer cells in order to verify the correlation between toxin exposure and cancer cell proliferation and invasion. In this review, we summarize the activation pathways of AFB1 and AFM1 and the data already reported in literature about their correlation with cancer development and progression. Moreover, considering that few data are still reported about what genes/proteins/miRNAs can be used as damage markers due to AFB1 and AFM1 exposure, we performed a bioinformatic analysis based on interaction network and miRNA predictions to identify a panel of genes/proteins/miRNAs that can be used as targets in further studies for evaluating the effects of the damages induced by AFB1 and AFM1 and their capacity to induce cancer initiation.

Highlights

Aflatoxins are secondary metabolites produced by different strains of fungi, like Aspergillus flavus and A. parasiticus, widely found as contaminants in a great variety of crops—cereals, oilseeds, tree nuts and spices
In this review, we decided: (i) to summarize the activation pathways of Aflatoxin B1 (AFB1) and Aflatoxin M1 (AFM1); (ii) to describe the data, already reported in literature, about their correlation with cancer development and progression; and (iii) to identify by a bioinformatic analysis a panel of genes/proteins/miRNAs that can be used as targets in further studies for evaluating the effects of the damages induced by AFB1 and AFM1 and their capacity to induce cancer initiation
It is important to underline that AFM1 is primarily considered a detoxification product of AFB1 metabolism, showing only 10% of mutagenicity compared to its precursor [39]

Summary

Introduction

Aflatoxins are secondary metabolites produced by different strains of fungi, like Aspergillus flavus and A. parasiticus, widely found as contaminants in a great variety of crops—cereals, oilseeds, tree nuts and spices. Indirect exposure to aflatoxins is another point of concern to human and animal health since these compounds can be transferred to offspring during gestation or lactation, or to other species upon the assumption of contaminated products like milk, eggs and meat. Immunoresponse modulation has been observed on murine macrophages after AFB1 exposure; some authors showed an anti-proliferative action not related to apoptotic pathways and a reduction in NO levels upon exposure to not cytotoxic concentrations [14] Another toxin causing great concern is Aflatoxin M1 (AFM1), the principal hydroxylated metabolite of AFB1, found in milk ( the designation M) of mammals fed upon contaminated feedstuff. (ii) to describe the data, already reported in literature, about their correlation with cancer development and progression; and (iii) to identify by a bioinformatic analysis a panel of genes/proteins/miRNAs that can be used as targets in further studies for evaluating the effects of the damages induced by AFB1 and AFM1 and their capacity to induce cancer initiation

Chemical Properties of AFB1 and AFM1

Principal

Liver Cancer

Lung Cancer

Findings

Gastrointestinal Cancer and Other Cancers