Assessment of Toxicity, Genotoxicity and Cytotoxicity of Phenylcycloalkanpolycarboxylic Acids: A Study with Allium cepa and Chlorella vulgaris

Objective: A complex approach using test organisms from different taxonomic groups (the unicellular green alga Chlorella vulgaris and the onion Allium cepa) was employed to assess the toxicity, cytotoxicity, and genotoxicity of polycarboxylic acids containing cycloaliphatic fragments. Methods: Onion (Allium cepa L.) of the Stuttgarter Riesen variety was used as a test object. Samples were analyzed using a Mikromed microscope (Russia) at 400× magnification. Differences were considered statistically significant at p < 0.05. The unicellular green alga Chlorella vulgaris (Beijer), strain LARG-1, obtained from the Vavilov Institute of General Genetics of the Russian Academy of Sciences, was used to investigate genotoxic effects. The culture was incubated in a Flora-1 photobioreactor (Russia) for 10 days at 25°C. Visible mutations were determined using an Altami stereomicroscope (Russia) at magnifications ranging from 15× to 40×. Results and Discussion: Polycarboxylic acids I–IV were evaluated at concentrations of 1.0%, 0.1%, 0.01%, and 0.001%. Compounds I and II at a concentration of 1.0% significantly inhibited the cell division rate, almost completely stopping it. Compounds I–IV at a concentration of 0.1% inhibited the cell division rate in the onion root meristem, reducing the mitotic index to 8.33 ± 1.12, 8.11 ± 0.90, 5.33 ± 0.70, and 8.33 ± 0.28%, respectively, compared to 11.05 ± 0.73% in the control. In contrast, compounds I–IV at concentrations of 0.01 and 0.001% did not cause a significant decrease in the mitotic index or observable damage to the root meristem. Analysis of the mitotic phase indices showed that compounds I–IV at a concentration of 1.0% exhibited antiproliferative activity. The tested polycarboxylic acids demonstrated mutagenic effects in the bioassay with Chlorella vulgaris. Conclusions: The analysis of the genotoxic activity polycarboxylic acids I–IV in various concentrations carried out using a system of toxicogenetic methods, showed that at high concentrations these compounds can reduce the mitotic index and phase indexes. Although no chromosomal aberrations were observed, the compounds demonstrated significant cytotoxicity and mutagenicity, as evidenced by the inhibition of cell division in Allium cepa and the increased mutation frequency in Chlorella vulgaris. The polycarboxylic acids I–IV with antiproliferative activity can be used as promising scaffolds. These drugs can be recommended for further research. The approach described here in may be applied for obtaining rapid, cost-efficient and useful supplementary data on different types of toxicity in vitro for promising scaffolds as well as for drugs under development.