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

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).