Rapidly evolving laser technologies have led to the development of laser-generated particle accelerators as an alternative to conventional facilities. However, the radiobiological characteristics need to be determined to enhance their applications in biology and medicine. In this study, the radiobiological effects of ultrashort pulsed electron beam (UPEB) and X-ray radiation in human lung fibroblasts (MRC-5 cell line) exposed to doses of 0.1, 0.5, and 1 Gy are compared. The changes of γH2AX foci number as a marker of DNA double-strand breaks (DSBs) were analyzed. In addition, the micronuclei induction and cell death via apoptosis were studied. We found that the biological action of UPEB-radiation compared to X-rays was characterized by significantly slower γH2AX foci elimination (with a dose of 1 Gy) and strong apoptosis induction (with doses of 0.5 and 1.0 Gy), accompanied by a slight increase in micronuclei formation (dose of 1 Gy). Our data suggest that UPEB radiation produces more complex DNA damage than X-ray radiation, leading to cell death rather than cytogenetic disturbance.
In silico (quantitative) structure–activity relationship modeling is an approach that provides a fast and cost-effective alternative to assess the genotoxic potential of chemicals. However, one of the limiting factors for model development is the availability of consolidated experimental datasets. In the present study, we collected experimental data on micronuclei in vitro and in vivo, utilizing databases and conducting a PubMed search, aided by text mining using the BioBERT large language model. Chemotype enrichment analysis on the updated datasets was performed to identify enriched substructures. Additionally, chemotypes common for both endpoints were found. Five machine learning models in combination with molecular descriptors, twelve fingerprints and two data balancing techniques were applied to construct individual models. The best-performing individual models were selected for the ensemble construction. The curated final dataset consists of 981 chemicals for micronuclei in vitro and 1309 for mouse micronuclei in vivo, respectively. Out of 18 chemotypes enriched in micronuclei in vitro, only 7 were found to be relevant for in vivo prediction. The ensemble model exhibited high accuracy and sensitivity when applied to an external test set of in vitro data. A good balanced predictive performance was also achieved for the micronucleus in vivo endpoint.
26 February 2025 in Mutation Research - Genetic Toxicology and Environmental Mutagenesis
Introduction: Plants containing β-sitosterol and oleamide are important for various diseases. So, Dillenia indica, D. obovata, and D. pentagyna were investigated for phytochemicals, cytotoxicity and genotoxicity levels on peripheral blood mononuclear cells (PBMCs) and Hela cells. The protective effect of D. pentagyna extract on a HepG2 cell line was also investigated. Methods: Gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC) were used for phytochemical analysis. 3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction (MTT) and comet assays were performed for toxicity testing and protective effects against DNA oxidative damage. Results: The major components were oleamide and β-sitosterol at 38.464-58.247% and 5.585- 6.887% with concentration and quantity of β-sitosterol at 0.2-0.37 mg/mL and 0.42-0.964 mg/g leaf. The D. indica, D. obovata, and D. pentagyna toxicities on PBMCs showed IC50 values at >430, >430, and 350 µg/mL respectively, with no significant DNA damage (P > 0.05) compared to the negative control group. All plant extracts showed toxic activity on Hela cell with IC50 values at <0.43 µg/mL and induced significant DNA damage (P < 0.05) compared to the negative control group. Conversely, the activity of the D. pentagyna extract indicated low cytotoxic activity against HepG2 (IC50>430 μg/mL), no significant (P > 0.05) DNA damage induction, significantly (P < 0.05) decreased DNA damage level, and tremendous antioxidant effect. Additionally, a combined mixture of all plants in an equal proportion revealed no IC50 value and insignificant DNA damage. Conclusion: All the studied species contained oleamide and β-sitosterol, with toxicity on Hela cells without toxicity on PBMC. The D. pentagyna species showed high antioxidant effects and no toxicity on HepG2.