Expression of the TR53 oncosuppressor gene modified with benzo[a]pyrene and the SARS-COV-2 vaccine antigen in an in vitro experiment

Introduction. The impact of chemical and biological environmental factors is associated with the risk of a genetic predisposition to the development of cardiovascular and cancer-associated diseases, which determines the relevance of the search for genetic indicator markers of early disorders in the mRNA structure.

Materials and methods. The analysis of TP53 rs1042522 gene polymorphism, as well as the relative normalized expression level of TP53 hs1034249_m1 transcript, in whole blood cell culture in healthy volunteers, both spontaneous and induced by 24-hour incubation with benzo[a]pyrene and SARS-CoV-2 vaccine antigen (at concentrations of 0.006 mg/ml), was conducted.

Results. Comparative analysis of spontaneous and antigen-induced levels of TP53 hs1034249_m1 mRNA expression allowed establishing individual and group values of relative expression associated with the polymorphism features of the TP53 rs1042522 gene. Benzo[a]pyrene and SARS-CoV-2 were found to have opposite effects on the expression of hs1034249_m1 TP53 genes in the case of the CG rs1042522 genotype, while the combined effect of benzo[a]pyrene and SARS-CoV-2, which reflected the inhibition of the expression of hs00900055_m1 of the TP53 gene was associated with the GG genotype.

The limitations of the study are the use of a relatively small sample and a limited number of whole blood samples.

Conclusion. The ability of benzo[a]pyrene and SARS-CoV-2 at concentrations of 6 µg/L to modify the expression of the TP53 apoptosis gene in vitro has been shown, which makes it possible to consider the increase in the expression of hs00900055_m1 of the TP53 gene induced by benzo[a]pyrene as one of the mechanisms for aggravating the course of viral infections (SARS-CoV-2) in connection with loss of p53-controlling for the development of inflammation (its proliferative phase) for owners of the heterozygous variant of CG TP53 rs1042522. In the case of variant monozygotic polymorphism GG TP53 rs1042522, the combination of benzo[a]pyrene and SARS-CoV-2 leads to inhibition of the expression of hs00900055_m1 mRNA of the TP53 gene, which is phenotypically reflected by the formation of asthenia, immunosuppression and onco-proliferative complications. The hs00900055_m1 transcript of the TP53 gene is recommended as an indicator for the tasks of diagnosing early disorders associated with the combination of SARS-CoV-2+ benzo[a]pyrene. The experiment simulates the natural conditions of real combinations of influencing factors.

Compliance with ethical standards. The study was performed in accordance with the World Medical Association’s Declaration of Helsinki “Ethical principles for conducting medical research involving people as subjects” and the National Standard of the Russian Federation GOST-R 52379-2005 “Good Clinical Practice” (ICH E6 GCP).

Contribution:
Dolgikh O.V. — the concept and design of the study, editing, responsibility for the integrity of all parts of the article;
Kazakova O.A. — concept and design of research, collection and processing of material, writing of text;
Zaitseva N.V. — editing, approval of the final version of the article.
All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version.

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

Acknowledgement. The study had no sponsorship.

Received: August 21, 2023 / Accepted: September 26, 2023 / Published: November 20, 2023