Aerogenic exposure of benzo(a)pyrene in children as the modification factor of genetically determined cell death

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Abstract

Introduction. The study of genetically determined cell death features in children under the conditions of aerogenic exposure to benzo(a)pyrene is relevant in the identification of immunological and genetic markers of technogenic chemical factor exposure.

Materials and methods. Five hundred sixty nine preschool children were examined. Observation group included 384 children living under the conditions of aerogenic exposure to benzo(a)pyrene. Comparison group consisted of 185 children living in a relatively clean area. Determination of the content of benzo(a)pyrene in atmospheric air and in blood was carried out by HPLC. Determination of Annexin-FITC+7AAD–, Annexin-FITC+7AAD+, Bax, Bcl-2, CD95+, p53, TNFR was made by flow cytofluorometry. The study of FAS (rs1159120) and TP53 (rs1042522) gene polymorphism was performed by real-time PCR.

Results. The aerogenic benzo(a)pyrene exposure (7.4 MPCad) at a dose of 0.000163 mg/(kg · day) causes an increase in the level of contamination in children blood relative to the comparison group and the reference level (p<0.05). Changes in the immune profile of the examined contingent (increased content of apoptosis markers — Annexin-FITC+7AAD–-cells, CD3+CD95+-lymphocytes, p53, TNFR against the background of compensatory anti-apoptotic protein Bcl-2 hyperproduction) are associated with the C-allele (OR=1.38; 95% CI: 1.02–1.88, p<0.05); and CC-genotype (OR=2.53; 95% CI: 1.72–3.72, p<0.05) of FAS gene (rs1159120), and the C-allele (OR=1.96; 95% CI: 1.53–2.53, p<0.05) and CC-genotype (OR=2.53; 95% CI: 1.72–3.72, p<0.05) of t TP53 gene (rs1042522).

Limitations. There are no restrictions on conducting research related to the possibility of using the selected methods and the characteristics of the objects of research.

Conclusion. Changes in the immune profile associated with blood contamination with benzo(a)pyrene (excess of AnnexinV-FITC+7AAD– and CD3+CD95+-lymphocytes, p53, TNFR, Bcl-2 cells) are associated with the C-allele (OR=1.38; 95% CI: 1.02–1.88, p<0.05); and CC-genotype (OR=2.53; 95% CI: 1.72–3.72, p<0.05) of FAS gene (rs1159120), and C-allele (OR=1.96; 95% CI: 1.53–2.53, p<0.05) and CC-genotype (OR=2.53; 95% CI: 1.72–3.72, p<0.05) of t TP53 gene (rs1042522) form the risks of programmed cell death violations in children living under the conditions of aerogenic exposure to benzo(a)pyrene, when it is entered the body at a dose of more than 0.000163 mg/(kg · day).

Compliance with ethical standards. The study was carried out in compliance with the ethical requirements of the Helsinki Declaration of the WMA 2000 and the Protocol of the Council of Europe Convention on Human Rights and Biomedicine 1999. The study was approved by the LEC of the Federal Scientific Center for Medical and Preventive Health Risk Management Technologies of the Federal Service for Supervision of Consumer Rights Protection and Human Well-Being (Protocol No. 23 of 12/20/2021). Informed consent was obtained for all participants.

Contribution:
Dolgikh O.V. — concept and design of research, writing and editing of text;
Nikonoshina N.A. — collection and processing of material, statistical processing, writing and editing of text.
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: March 9, 2023 / Accepted: May 31, 2023 / Published: June 20, 2023

About the authors

Oleg V. Dolgikh

Federal Scientific Center for Medical and Preventive Health Risk Management Technologies of Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing

Author for correspondence.
Email: noemail@neicon.ru
ORCID iD: 0000-0003-4860-3145
Russian Federation

Natalya A. Nikonoshina

Federal Scientific Center for Medical and Preventive Health Risk Management Technologies of Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing

Email: nat08.11@yandex.ru
ORCID iD: 0000-0001-7271-9477

Junior research associate of the laboratory of immunology and allergology, post-graduate student of the Federal Scientific Center for Medical and Preventive Health Risk Management Technologies, Perm, 614045, Russian Federation.

e-mail: nat08.11@yandex.ru

Russian Federation

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