Work

Aflatoxin B1: from metabolism to multi-organ carcinogenesis

Year: 2026

Type: review

Abstract: Aflatoxin B1 (AFB1), a Group 1 carcinogen classified by the International Agency for Research on Cancer, chronically exposes a substantial proportion of the global population through dietary intake, primarily from fungal contamination of staple crops such as maize and peanuts. Climate change is progressively expanding this problem beyond its traditional tropical and subtropical boundaries into temperate regions of Europe and Asia. The carcinogenicity of AFB1 is initiated by its metabolic activation via hepatic cytochrome P450 enzymes, yielding AFBO, which forms DNA adducts and subsequently induces the signature G-to-T transversion mutation at codon 249 of TP53. However, recent evidence indicates that this canonical pathway represents only part of a far more complex picture. This review advances three interconnected themes. First, the aryl hydrocarbon receptor (AHR) has been established as an upstream regulatory hub of AFB1 toxicity, both driving CYP-mediated metabolic activation and mediating PD-L1 upregulation to promote immune evasion. Second, oxidative stress, epigenetic reprogramming, and autophagic dysfunction operate as accelerators that drive malignant transformation. Third, the multi-organ toxicity of AFB1, encompassing intestinal barrier disruption, systemic immunosuppression, and renal and reproductive toxicity, together with its co-exposure with hepatitis B virus and other mycotoxins, is expanding our traditional understanding of synergistic carcinogenesis. On the translational front, this review integrates the biomarker continuum from exposure (AFB1-albumin adducts) through effect (TP53 mutation, epigenetic marks) to susceptibility (GST/CYP genotypes, GNMT, CDKN2A), and synthesizes a multi-tiered intervention framework spanning source control, chemoprevention (AHR inhibitors, antioxidants), microbial/enzymatic detoxification, and precision immunotherapy (Figure 1(Fig. 1)).

Source: EXCLI journal

DOI: 10.17179/excli2026-9793