Multi-Endpoint Toxicological Assessment of the Food Additive Triammonium Citrate: Differential Responses in Colorectal Cancer Cells and Non-Neoplastic Colon Fibroblasts
Journal of Applied Toxicology, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Basım Tarihi: 2026
- Doi Numarası: 10.1002/jat.70461
- Dergi Adı: Journal of Applied Toxicology
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Applied Science & Technology Source, BIOSIS, Chemical Abstracts Core, Chimica, EMBASE, Environment Index, MEDLINE, Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest)
- Anahtar Kelimeler: clonogenic survival, colorectal carcinoma, comet assay, cytotoxicity, E380, food additive, genotoxicity, micronucleus, triammonium citrate, wound closure
- Çukurova Üniversitesi Adresli: Evet
Özet
Triammonium citrate (TAC; E380) is used as a food additive, making characterization of its effects in malignant and non-neoplastic colon-derived cells relevant to applied toxicology. We conducted a multi-endpoint assessment of 0.5- to 2.0-mg/mL TAC in KRASG13D-mutant, mismatch repair-deficient HCT116 colorectal carcinoma cells and non-neoplastic CCD-18Co colon fibroblasts. Exposure durations were endpoint-specific (60 min, 24 h, or 48 h), and endpoints included viability, primary DNA damage, micronucleus frequency, nuclear division, clonogenic survival, and wound closure. Microbial assays tested antimicrobial and membrane-disruptive activity; docking was exploratory. The clearest differential response occurred at 2.0 mg/mL after 48 h, when viability was 8.80% ± 2.14% in HCT116 cells and 49.52% ± 11.50% in CCD-18Co cells. Primary DNA damage increased in both models, with the largest numerical comet response in HCT116 cells at 2.0 mg/mL. HCT116 clonogenic survival decreased to 29.0% ± 4.8% at 2.0 mg/mL after a 24-h exposure and 9-day recovery. Micronucleus frequency did not increase in either cell line, although the nuclear division index decreased in both at 2.0 mg/mL after 48 h, indicating cytostasis. TAC also reduced wound closure in both models. No microbial growth inhibition was detected at 0.5–2.0 mg/mL, and no membrane leakage was detected in Staphylococcus aureus up to 200 mg/mL. Docking generated hypotheses involving PFK-1, KRAS, and PARP-1 but did not establish binding or target engagement. Collectively, these findings demonstrate pronounced HCT116 cytotoxicity together with primary DNA damage in both models, without detectable chromosome-level damage, and provide a basis for mechanistic investigation.