<p>Aflatoxin B1 (AFB1) is a highly toxic mycotoxin produced by filamentous fungi of the genus <i>Aspergillus</i>, which frequently colonize crops of major economic and nutritional importance during growth, harvest, and storage. Consequently, AFB1 contamination represents a significant threat to global food safety and security. Following ingestion, AFB1 undergoes hepatic bioactivation by cytochrome P450 enzymes, mainly CYP3A4 and CYP1A2, yielding the highly reactive intermediate aflatoxin B1-8,9-epoxide (AFBO). This electrophilic metabolite forms covalent adducts with proteins and DNA, thereby disrupting cellular homeostasis and promoting hepatocarcinogenesis. In particular, AFBO-induced DNA adducts, such as AFB1-N7-dGua and its secondary lesion AFB1-FAPY, drive G-to-T transversions in key genes, including p53 and <i>ras</i>, contributing to genomic instability and compromised DNA repair capacity. These molecular events are further exacerbated by AFB1-induced oxidative stress, chronic inflammation, and epigenetic dysregulation, including hypermethylation-mediated silencing of tumor suppressor genes, altered microRNA expression, and disruption of cellular senescence pathways. In response to these challenges, multiple mitigation strategies, many still under development, have been proposed, including the reinforcement of food safety regulations, vaccination against hepatitis B virus (HBV), the application of beneficial microorganisms as biocontrol agents (e.g., <i>Bacillus subtilis</i>), the use of non-toxigenic <i>Aspergillus</i> spp. strains and the application of various chemo-protective compounds capable of mitigating the harmful effects of aflatoxicosis. These efforts underscore the urgent need for integrated approaches aimed at reducing AFB1 exposure, strengthening food safety systems, and improving global public health outcomes.</p>

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Aflatoxin B1 and food safety: Mechanisms of action associated to Hepatocellular Carcinoma

  • Mariana C. Zamudio,
  • Daniel Balleza

摘要

Aflatoxin B1 (AFB1) is a highly toxic mycotoxin produced by filamentous fungi of the genus Aspergillus, which frequently colonize crops of major economic and nutritional importance during growth, harvest, and storage. Consequently, AFB1 contamination represents a significant threat to global food safety and security. Following ingestion, AFB1 undergoes hepatic bioactivation by cytochrome P450 enzymes, mainly CYP3A4 and CYP1A2, yielding the highly reactive intermediate aflatoxin B1-8,9-epoxide (AFBO). This electrophilic metabolite forms covalent adducts with proteins and DNA, thereby disrupting cellular homeostasis and promoting hepatocarcinogenesis. In particular, AFBO-induced DNA adducts, such as AFB1-N7-dGua and its secondary lesion AFB1-FAPY, drive G-to-T transversions in key genes, including p53 and ras, contributing to genomic instability and compromised DNA repair capacity. These molecular events are further exacerbated by AFB1-induced oxidative stress, chronic inflammation, and epigenetic dysregulation, including hypermethylation-mediated silencing of tumor suppressor genes, altered microRNA expression, and disruption of cellular senescence pathways. In response to these challenges, multiple mitigation strategies, many still under development, have been proposed, including the reinforcement of food safety regulations, vaccination against hepatitis B virus (HBV), the application of beneficial microorganisms as biocontrol agents (e.g., Bacillus subtilis), the use of non-toxigenic Aspergillus spp. strains and the application of various chemo-protective compounds capable of mitigating the harmful effects of aflatoxicosis. These efforts underscore the urgent need for integrated approaches aimed at reducing AFB1 exposure, strengthening food safety systems, and improving global public health outcomes.