The Cytotoxicity of Cyanuric Acid and Certain Derivatives in Vitro

Authors

  • Tsvetelina Batsalova Department of Developmental Biology, Plovdiv University, Plovdiv 4000, Bulgaria
  • Desislava Kolchakova Department of Developmental Biology, Plovdiv University, Plovdiv 4000, Bulgaria
  • Balik Dzhambazov Department of Developmental Biology, Plovdiv University, Plovdiv 4000, Bulgaria

DOI:

https://doi.org/10.17140/TFMOJ-3-125

Keywords:

Cyanuric acid, Trichloroisocyanuric acid, 1,3,5-tris(2-hydroxyethyl) isocyanurate, In vitro cytotoxicity, Cancer cell lines, Fibroblasts

Abstract

Background
The s-triazine category includes cyanuric acid and its derivatives. They are widely used in industry, mostly in the manufacturing of disinfectants, bleaching agents, and pesticides. According to recent findings, cyanuric acid alone has a low overall cytotoxicity, but when combined with melamine, it has a large unfavorable effect. Nevertheless, assessments of cyanuric acid toxicity against several human cell types have not been carried out utilizing a panel of in vitro experiments. Furthermore, the cytotoxicity and possible anticancer effects of several cyanuric acid derivatives, such as 1,3,5-tris(2-hydroxyethyl) isocyanurate and trichloroisocyanuric acid, are poorly understood.
Aim
To use various cancer cell lines and healthy fibroblasts to examine the toxicity of cyanuric acid, trichloroisocyanuric acid, and 1,3,5-tris(2-hydroxyethyl) isocyanurate.
Materials and Procedures
The in vitro cytotoxicity of cyanuric acid, trichloroisocyanuric acid, and 1,3,5-tris(2-hydroxyethyl) isocyanurate was assessed using MTT, Neutral Red, and Clonogenic assays. Three cancer cell lines (HeLa, A549, and CaOV) as well as healthy human fibroblasts were used to test various doses of the chemicals. We computed and compared IC50 values. Following exposure to cyanuric acid, trichloroisocyanuric acid, and 1,3,5-tris(2-hydroxyethyl) isocyanurate, intracellular ATP measurements and microscopic assessments of cellular shape were carried out.
Findings
Trichloroisocyanuric acid (TCIC) showed the highest in vitro cytotoxicity of the three test agents. It's interesting to note that MTT experiments showed that TCIC's harmful effects were mostly focused on cancer cells that had mitochondrial dysfunction. The presence of modest concentrations of triazine fully suppressed the clonogenicity of cancer cell lines. Both cancer cells and normal fibroblasts' shape and intracellular ATP levels were affected by TCIC exposure, however the effects were more pronounced in cancer cells.
Conclusion
The studied chemicals' cytotoxicity is arranged as follows: 1,3,5-tris(2-hydroxyethyl) isocyanurate > cyanuric acid > trichloroisocyanuric acid. The anticancer action of trichloroisocyanuric acid is selective.

References

Quirke ME. 1,3,5-Triazines. In: Katritzky AR, Rees CW (eds). Comprehensive Heterocyclic Chemistry III. Oxford, New York: Pergam-on Press. 1984.

Bartholomew D. 1,3,5-Triazines. In: Boulton AJ (eds). Compre-hensive Heterocyclic Chemistry II. Oxford, New York: Pergamon Press. 1996.

Budnowski M. Preparation and properties of the diastereoiso-meric 1,3,5-triglycidyl-s-triazinetriones. Agnew Chem. 1968; 7: 827- 828. doi: 10.1002/anie.196808271

Fischer H, Zeidler U, Budnowski M, et al. Investigation of the antitumor activity of new epoxide derivatives. Part I: s-Triazinetri-one derivatives. Arzneimittelforschung. 1984; 34(5): 543-547

Allen LM, Briggle TV, Pfaffenberger CD. Absorption and excre-tion of cyanuric acid in long-distance swimmers. Drug Metab Rev. 1982; 13(3): 499-516. doi: 10.3109/03602538209029992

Hammond BG, Barbee SJ, Inoue T, et al. A review of toxicology studies on cyanurate and its chlorinated derivatives. Environ Health Perspect. 1986; 69: 287-292. doi: 10.1289/ehp.8669287

Sun H, Wang K, Wei H, Li Z, Zhao H. Cytotoxicity, organ distribution and morphological effects of melamine and cyanu-ric acid in rats. Toxicol Mech Methods. 2016; 26(7): 501-510. doi: 10.1080/15376516.2016.1201559

Dobson RL, Motlagh S, Quijano M, et al. Identification and characterization of toxicity of contaminants in pet food leading to an outbreak of renal toxicity in cats and dogs. Toxicol Sci. 2008; 106(1): 251-262. doi: 10.1093/toxsci/kfn160

Liu X, Huang da W, Wu KJ, et al. An evaluation of genotoxicity and cytotoxicity of melamine in combination with cyanuric acid at three mass ratios. Biomed Environ Sci. 2014; 27(8): 641-645. doi:

3967/bes2014.098 10. Loveday KS, Anderson BE, Resnick MA, Zeiger E. Chromo-some aberration and sister chromatid exchange tests in Chinese hamster ovary cells in vitro. V: Results with 46 chemicals. Environ Mol Mutagen. 1990; 16(4): 272-303.

Tilstam U, Weinmann H. Trichloroisocyanuric acid: A safe and efficient oxidant. Org Proc Res Dev. 2002; 6(4): 384-393. doi: 10.1021/op010103h

Sanchez-Fortun S, Llorente MT, Castano A. Cytotoxic and genotoxic effect in RTG-2 cell line exposed to selected biocides used in the disinfection of cooling towers. Ecotoxicology. 2008; 17(4): 273-279. doi: 10.1007/s10646-008-0194-0

Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Im-Submit your article to this journal | https://openventio.org/submit-manuscript/ munol Methods. 1983; 65(1-2): 55-63.

Repetto G, del Peso A, Zurita JL. Neutral red uptake assay for the estimation of cell viability/cytotoxicity. Nat Protoc. 2008; 3(7): 1125-1131. doi: 10.1038/nprot.2008.75

Fotakis G, Timbrell JA. In vitro cytotoxicity assays: Compari-son of LDH, neutral red, MTT and protein assay in hepatoma cell lines following exposure to cadmium chloride. Toxicol Lett. 2006; 160(2): 171-177. doi: 10.1016/j.toxlet.2005.07.001

Munshi A, Hobbs M, Meyn RE. Clonogenic cell survival as-say. Methods Mol Med. 2005; 110: 21-28. doi: 10.1385/1-59259-869- 2:021

Marques SM, Esteves da Silva JC. Firefly bioluminescence: A mechanistic approach of luciferase catalyzed reactions. IUBMB life. 2009; 61(1): 6-17. doi: 10.1002/iub.134

Hoz A, Sánchez-Migallón A. Green synthesis of 1,3,5-triazines with applications in supramolecular and materials chemistry. Tar-gets in Heterocyclic Systems. 2017; 20: 139-173. doi: 10.17374/tar-gets.2017.20.140

Zeiger E, Anderson B, Haworth S, et al. Salmonella mutagen-icity tests: III. Results from the testing of 255 chemicals. Environ Mutagen. 1987; 9: 1-109.

Zeiger E, Anderson B, Haworth S, Lawlor T, Mortelmans K. Salmonella mutagenicity tests: V. Results from the testing of 311 chemicals. Environ Mol Mutagen. 1992; 19(21): 2-141.

Singla P, Luxami V, Paul K. Triazine as a promising scaffold for its versatile biological behavior. Eur J Med Chem. 2015; 102: 39-57. doi: 10.1016/j.ejmech.2015.07.037

Downloads

Published

2023-11-23

How to Cite

Tsvetelina Batsalova, Desislava Kolchakova, & Balik Dzhambazov. (2023). The Cytotoxicity of Cyanuric Acid and Certain Derivatives in Vitro. Toxicology and Forensic Medicine, 8(1), 14–21. https://doi.org/10.17140/TFMOJ-3-125

Similar Articles

1 2 3 > >> 

You may also start an advanced similarity search for this article.