Contamination of biomedia with N-nitrosamines as a factor in the development of disorders of the immune status in schoolchildren with dyspepsia under conditions of altered polymorphism of candidate genes

Introduction. Contamination of drinking water sources with N-nitrosamines, substances of the first class of danger, creates conditions for the development of disorders of the immune profile in primary school-age children with diseases of the digestive system. Bio- and toxicokinetic features of these substances, when they enter the body with water, form changes on the part of the immune system, and the biodegradation of these substances by enzymes of the first phase of detoxification of the CYP450 family is accompanied by the formation of direct carcinogens capable of DNA methylation, which is characterized by dyspepsia, uncontrolled cell proliferation in the conditions of the CC genotype of the gene of the detoxification enzyme CYP1A1_3 rs4646421.

Materials and methods. The study involved fifty two children of primary school age (6-12 years old) living in the Perm Territory, consuming water from underground sources characterized by pollution with N-nitrosamines. The observation group included 30 children with pathology of the digestive system. The comparison group consisted of 22 conditionally healthy children. Chemical (NDMA, NDEA), immunological (IgE specific to NDMA, IgM, CD95⁺, IL 10, Bcl, cortisol, CA 72-4), and genetic (gene of the detoxification enzyme CYP1A1_3 rs4646421) studies of the biological environment were performed for all children.

Results. According to the results of the conducted studies, it was found that the observation group relative to the comparison group was characterized by an increased content of N-nitrosamines in the blood up to 3.8 times; altered immune status in the form of an increase in specific sensitization to NDMA by 1.2 times, inhibition of apoptotic activity of CD95⁺ markers by 1.8 times (p<0.05) and Bcl2 by 1.3 times, a decrease in the level of expression of the anti-inflammatory cytokine IL10 by 2.3 times (p<0.05), an increase in the expression of the stress hormone cortisol by 1.3 times (p<0.05) and the cancer marker CA 72-4 by 2.5 times; an increase in the frequency of the wild homozygous CC genotype of the CYP1A1_3 rs4646421 gene by 1.5 times, which acted as a risk factor for dyspepsia in conditions of blood contamination with N-nitrosamines (OR=4.5; CI: 1.16-17.40, p<0.05).

Limitations. The limitation lies in the use of the identified markers for the diagnosis of immune disorders manifested by blood contamination with nitrosamines in a specific area.

Conclusion. The obtained results indicate to an imbalance of the immune profile in conditions of low-level chronic oral intake of N-nitrosamines with a genetic predisposition to the development of toxic effects. So far, the detected violations should be attributed to early signs indicating the formation of dyspepsia in schoolchildren consuming water from underground sources contaminated with N-nitrosamines.

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).

Patient consent. Each participant of the study (or his/her legal representative) gave informed voluntary written consent to participate in the study and publish personal medical information in an impersonal form in the journal "Gigiena i Sanitariya (Hygiene and Sanitation, Russian journal)".

Contribution:
Kazakova O.A. — the concept and design of the study, the collection and processing of the material, writing text, editing, approval of the final version of the article, responsibility for the integrity of all parts of the article;
Yaroma A.V. — the collection and processing of the material, writing text;
Dolgikh O.V. — writing text, editing, approval of the final version of the article, responsibility for the integrity of all parts of the article.

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

Acknowledgement. The study had no sponsorship. 

Received: September 6, 2022 / Accepted: October 3, 2022 / Published: November 30, 2022