Several reports have shown antimicrobial and anticancer activities of mucous glycoproteins extracted from the giant African snail Achatina fulica. Anticancer properties of the snail mucous peptides remain incompletely revealed. The aim of this study was to predict anticancer peptides from A. fulica mucus. Two of HPLC-separated mucous fractions (F2 and F5) showed in vitro cytotoxicity against the breast cancer cell line (MCF-7) and normal epithelium cell line (Vero). According to the mass spectrometric analysis, 404 and 424 peptides from the F2 and F5 fractions were identified. Our comprehensive bioinformatics workflow predicted 16 putative cationic and amphipathic anticancer peptides with diverse structures from these two peptidome data. These peptides would be promising molecules for new anti-breast cancer drug development.

DNA-methylating environmental carcinogens such as N-nitrosodimethylamine (NDMA) and certain alkylators used in chemotherapy form O⁶-methylguanine (m6G) as a functionally critical intermediate. NDMA is a multi-organ carcinogen found in contaminated water, polluted air, preserved foods, tobacco products, and many pharmaceuticals. Only ten weeks after exposure to NDMA, neonatally-treated mice experienced elevated mutation frequencies in liver, lung and kidney of ∼35-fold, 4-fold and 2-fold, respectively. High-resolution mutational spectra (HRMS) of liver and lung revealed distinctive patterns dominated by GC→AT mutations in 5’-Pu-G-3’ contexts, very similar to human COSMIC mutational signature SBS11. Commonly associated with alkylation damage, SBS11 appears in cancers treated with the DNA alkylator temozolomide (TMZ). When cells derived from the mice were treated with TMZ, N-methyl-N-nitrosourea, and streptozotocin (two other therapeutic methylating agents), all displayed NDMA-like HRMS, indicating mechanistically convergent mutational processes. The role of m6G in shaping the mutational spectrum of NDMA was probed by removing MGMT, the main cellular defense against m6G. MGMT-deficient mice displayed a strikingly enhanced mutant frequency, but identical HRMS, indicating that the mutational properties of these alkylators is likely owed to sequence-specific DNA binding. In sum, the HRMS of m6G-forming agents constitute an early-onset biomarker of exposure to DNA methylating carcinogens and drugs.

Aflatoxin B₁ (AFB₁) and sterigmatocystin (ST) are mycotoxins that pose significant threats to human and animal health owing to their mutagenic, carcinogenic, and toxic properties. They are structurally similar and widely believed to exert their biological effects via the generation of DNA-damaging epoxides at their respective terminal furan rings. Despite structural identity in the warhead portion of each toxin, this work shows that distal parts of each molecule are responsible for the distinctive mutational fingerprints seen in gptΔ C57BL/6J mouse embryo fibroblasts (MEFs). The two toxins differ structurally in the puckered cyclopentenone ring of AFB₁ and in the planar xanthone functionality of ST. While both toxins mainly induce GC→TA mutations, the aforementioned differences in structure apparently trigger unique patterns of mutations, as revealed by high-resolution duplex sequencing of MEF genomes. AFB₁ is more mutagenic than ST and displays its transversion mutations in a pattern with primary and secondary hotspots (underscored) in 5′-CGC-3′ and 5′-CGG-3′ contexts, respectively. ST displays a modest 5′-CGG-3′ hotspot while its other GC→TA transversions are more uniformly distributed in a pattern resembling established oxidative stress mutational spectra. This research delineates the mutational spectra of AFB₁ and ST, establishing these patterns as possible early-onset biomarkers of exposure.