Changes in apoptotic gene expression in the liver of laboratory animals following subchronic exposure to phenol and/or benzene

Introduction. Benzene and phenol are widespread toxins that enter the environment with industrial emissions, being typical representatives of coke production, as well as automobile exhaust and tobacco smoke. Their impact poses risks to public health and especially to industrial workers. The toxicity of these compounds is associated with the induction of oxidative stress, which can cause cell apoptosis. Studying the effects of benzene and phenol on the expression of genes regulating apoptosis in the liver is important for identifying the mechanisms of toxicity and searching for early biomarkers of response.

The study aims to explore changes in the expression of the p53, casp3, and casp9 genes in the liver of laboratory animals exposed to subchronic effects of phenol and/or benzene to clarify the mechanism of their isolated and combined effects.

Materials and methods. The authors conducted an experiment on white female rats, which were divided into 4 groups: "Benzene", "Phenol", "Benzene+Phenol" and "Control", 10 individuals each. The researchers carried out intoxication by intragastric administration 3 times a week for 4 weeks in a single dose of benzene — 100 mg/kg b.w. and phenol 15.85 mg/kg b.w. At the end of the experiment, the authors performed a complete decapitation of the animals and, for the analysis of gene expression, liver fragments were fixed, followed by the isolation of RNA, on the matrix of which cDNA was synthesized. The expression level of the casp3, casp9, and p53 genes was determined by quantitative real-time PCR. The scientists have conducted statistical analysis of the data using the Mann–Whitney U-test in the Statistica (StatSoft) program.

Results. The expression level of the p53 gene was significantly lower by 2.86 times in the "Benzene+Phenol" group of animals compared with the control group (p=0.0095). There was also a tendency to decrease the level of p53 expression in the liver in the group of animals exposed only to benzene, but it did not reach the level of statistical significance (p=0.057). The expression of the casp3 and casp9 genes did not significantly differ between the experimental groups and the control.

Limitations. The study was performed on female Wistar rats without taking into account possible intersex differences.

Conclusion. The combined administration of benzene and phenol suppresses the expression of the p53 gene in the liver of animals without changing the expression of the casp3 and casp9 genes, which may indicate a violation of the p53-dependent pathway of apoptosis. Further studies are needed to clarify the mechanisms of toxicity.

Ethics. Ethics approval was provided by the Ethics Committee of the Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers (protocol No. 2 of January 11, 2024).

Contributions:
Kikot A.M. — collecting material and data processing, writing text;
Bereza I.A. — collecting material and data processing, writing text;
Shaikhova D.R. — collecting material and data processing, writing text;
Sutunkova M.P. — research concept and design, editing;
Minigalieva I.A. — concept and design of research, editing;
Shabardina L.V. — collection of material and data processing, editing.

Funding. The study had no funding.

Conflict of interest. The authors declare no conflict of interest.

Received: 02.10.2025 / Accepted: 02.12.2025 / Published: 20.12.2025

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