Composition of the sputum bacterial microbiome of patients with different pathomorphological forms of non-small-cell lung cancer.

Recent studies have shown that the bacterial microbiome of the respiratory tract influences the development of lung cancer. Changes in the composition of the microbiome are observed in patients with chronic inflammatory processes. Such microbiome changes may include the occurrence of bacteria that cause oxidative stress and that are capable of causing genome damage in the cells of the host organism directly and indirectly. To date, the composition of the respiratory microbiome in patients with various histological variants of lung cancer has not been studied. In the present study, we determined the taxonomic composition of the sputum microbiome of 52 patients with squamous cell carcinoma of the lung, 52 patients with lung adenocarcinoma and 52 healthy control donors, using next-generation sequencing (NGS) on the V3-V4 region of the bacterial gene encoding 16S rRNA. The sputum microbiomes of patients with different histological types of lung cancer and controls did not show significant differences in terms of the species richness index (Shannon); however, the patients differed from the controls in terms of evenness index (Pielou). The structures of bacterial communities (beta diversity) in the adenocarcinoma and squamous cell carcinoma groups were also similar; however, when analyzed according to the matrix constructed by the Bray-Curtis method, there were differences between patients with squamous cell carcinoma and healthy subjects, but not between those with adenocarcinoma and controls. Using the LEFse method it was possible to identify an increase in the content of Bacillota (Streptococcus and Bacillus) and Actinomycetota (Rothia) in the sputum of patients with squamous cell carcinoma when compared with samples from patients with adenocarcinoma. There were no differences in the content of bacteria between the samples of patients with adenocarcinoma and the control ones. The content of representatives of the genera Streptococcus, Bacillus, Peptostreptococcus (phylum Bacillota), Prevotella, Macellibacteroides (phylum Bacteroidota), Rothia (phylum Actinomycetota) and Actinobacillus (phylum Pseudomonadota) was increased in the microbiome of sputum samples from patients with squamous cell carcinoma, compared with the control. Thus, the sputum bacterial microbiome of patients with different histological types of non-small-cell lung cancer has significant differences. Further research should be devoted to the search for microbiome biomarkers of lung cancer at the level of bacterial species using whole-genome sequencing.

Genetic damage in lymphocytes of lung cancer patients is correlated to the composition of the respiratory tract microbiome.

Recent findings indicate that the microbiome may have significant impact on the development of lung cancer by its effects on inflammation, dysbiosis or genome damage. The aim of this study was to compare the sputum microbiome of lung cancer (LC) patients with the chromosomal aberration (CA) and micronuclei (MN) frequency in peripheral blood lymphocytes. In the study, the taxonomic composition of the sputum microbiome of 66 men with untreated LC were compared with 62 control subjects with respect to CA and MN frequency and centromere fluorescence in situ hybridisation analysis. Results showed a significant increase in CA (4.11 ± 2.48% versus 2.08 ± 1.18%) and MN (1.53 ± 0.67% versus 0.87 ± 0.49%) frequencies, respectively, in LC patients as compared to control subjects. The higher frequency of centromeric positive MN of LC patients was mainly due to aneuploidy. A significant increase in Streptococcus, Bacillus, Gemella and Haemophilus in LC patients was detected, in comparison to the control subjects while 18 bacterial genera were significantly reduced, which indicates a decrease in the beta diversity in the microbiome of LC patients. Although, the CA frequency in LC patients is significantly associated with an increased presence of the genera Bacteroides, Lachnoanaerobaculum, Porphyromonas, Mycoplasma and Fusobacterium in their sputum, and a decrease for the genus Granulicatella after application of false discovery rate correction, significance was not any more present. The decrease of MN frequency of LC patients is significantly associated with an increase in Megasphaera genera and Selenomonas bovis. In conclusion, a significant difference in beta diversity of microbiome between LC and control subjects and association between the sputum microbiome composition and genome damage of LC patients was detected, thus supporting previous studies suggesting an etiological connection between the airway microbiome and LC.

Taxonomic diversity of sputum microbiome in lung cancer patients and its relationship with chromosomal aberrations in blood lymphocytes.

Here we report a pilot-sized study to compare the taxonomic composition of sputum microbiome in 17 newly-diagnosed lung cancer (LC) patients and 17 controls. Another object was to compare the representation of individual bacterial genera and species in sputum with the frequency of chromosomal aberrations in the blood lymphocytes of LC patients and in controls. Both groups were male; average age 56.1 ± 11.5 in patients and 55.7 ± 4.1 in controls. Differences in the species composition of bacterial communities in LC patients and controls were significant (pseudo-F = 1.94; p = 0.005). Increased prevalence in LC patients was detected for the genera Haemophilus and Bergeyella; whereas a decrease was observed for the genera Atopobium, Stomatobaculum, Treponema and Porphyromonas. Donors with high frequencies of chromosomal aberrations had a significant reduction in the microbiome of representatives of the genus Atopobium in the microbiome and a simultaneous increase in representatives of the species Alloprevotella compared to donors with a low level of chromosomal aberrations in lymphocytes. Thus, a comparison of the bacterial composition in the sputum of donors with cytogenetic damages in theirs lymphocytes, warrants further investigations on the potential role of microorganisms in the process of mutagenesis in somatic cells of the host body.

Induction and modulation of genotoxicity by the bacteriome in mammals.

The living environment is a multilevel physical and chemical xenobiotic complex with potentially mutagenic effects and health risks. In addition to inorganic exposures, all terrestrial and aquatic living forms interact with microbiota as selectively established communities of bacteria, viruses and fungi. Along these lines, the human organism should then be considered a "meta-organism" with complex dynamics of interaction between the environment and microbiome. Bacterial communities within the microbiome, bacteriome, by its mass, symbiotic or competitive position and composition are in a fragile balance with the host organisms and have a crucial impact on their homeostasis. Bacteriome taxonomic composition is modulated by age, sex and host genetic profile and may be changed by adverse environmental exposures and life style factors such as diet or drug intake. A changed and/or misbalanced bacteriome has genotoxic potential with significant impact on the pathogenesis of acute, chronic and neoplastic diseases in the host organism. Bacteria may produce genotoxins, express a variety of pathways in which they generate free radicals or affect DNA repair causing genome damage, cell cycle arrest and apoptosis, modulate immune response and launch carcinogenesis in the host organism. Future investigations should focus on the interplay between exposure to xenobiotics and bacteriome composition, immunomodulation caused by misbalanced bacteriome, impact of the environment on bacteriome composition in children and its lifelong effect on health risks.

[Cytogenetic effects in the population in agricultural regions of the Kemerovo region].

There was performed an analysis of chromosomal aberrations in peripheral blood lymphocytes of the inhabitants of 9 settlements from 6 agricultural regions of the Kemerovo region. 267 children-adolescents and 124 adults not involved in the industry were examined. The average level of chromosomal aberrations was 2.65% in children and 3.35% in adults. It can be regarded as a background regional level. There was no revealed the modifying ability of such factors as gender age, presence of harmful habits (smoking) on the formation of the frequency of cytogenetic abnormalities in residents of rural areas of the Kemerovo region.

[Role of repair gene polymorphism in estimating the sensitivity of human genome to radon in concentrations exceeding maximum permissible level].

The paper gives the results of investigating chromosome aberrations in human peripheral blood lymphocytes due to DNA repair genes, such as hOGG1, ADPRT, APE1, XRCC1, XpG, XpC, XpD, and NBS1, upon long-term exposure to excess indoor radon concentrations. The frequency of chromosome aberrations was found to be significantly lower in the carriers of the genotype hOGG1 326 Ser/Ser (versus the variant Ser/Cys), APE1 148 Asp/Asp (versus Val/Ala and Ala/Ala). The study polymorphic systems were shown to be of value in giving rise to individual types of chromosome aberrations (single fragments and chromosome exchanges).

[Contribution of genetic polymorphism to the formation of individual genome sensitivity in workers engaged in heat and power industry].

The paper presents the results of investigating an association between the frequency of chromosome aberrations and the CYP1A1, CYP1A2*1F GSTM1, and GSTT1 genes involved in xenobiotic biotransformation in workers engaged in heat and power engineering. The group of workers is shown to have a significantly higher rate of metaphases with aberrations (4.03 +/- 0.17%; n = 231) than the control group (2.06 +/- 0.17%; n = 141). Cytogenetic disorders are not found to depend on gender, age, and length of service. The study indicated that the level of chromosome aberrations was significantly higher in carriers of the CTP1A1 C/C, GSTM1 0/0 and GSTT1 0/0 genotypes. In individuals with a combination of the GSTM1 0/0 and GSTT1 0/0 genotypes, the level of chromosome aberrations was ascertained to be significantly higher than that in those with the protective form of these genes.

[Spread of carcinogenic and mutagenic effects in the population of Gornaia Shoria].

Mutagenic and carcinogenic effects were studied in the population of Gornaya Shoria, Kemerovo Region. The carcinogenic effects were evaluated on the basis of the data given by the Kemerovo regional cancer registry over 1990-2008. The standardized cancer morbidity index in Gornaya Shoria (342 per 100,000 population) exceeded the average index in the Kemerovo Region (286 per 100,000) in the same period. The mutagenic effects were estimated on the basis of the monitoring data on the frequency and spectrum of chromosomal aberrations in the peripheral blood lymphocytes of the dwellers of Gornaya Shoria for the 1992-2009 period. The mean level of chromosomal aberrations (5.31%) in the residents of Gornaya Shoria was found to be greater than the regional background mutation rate (2.86%) (p < 0.001). The values of individual aberration types (chromatid and chromosomal breaks, as well as chromosome-type exchange aberrations) were significantly higher in the dwellers of Gornaya Shoria than those in the basic control group. The revealed high mutagenic load in the inhabitants of Tashtagol District, Kemerovo Region, allows this area to be assigned to high genetic risk ones.

[Toxic and genetic risk assessments in children of Gornaya Shoria].

This comprehensive study assessed a number of environmental factors that were potentially able to induce genotoxic effects in man. A set of radiological, physicochemical, and bioindication techniques was used to estimate the quality of water, air, and soil in the places of residence and education of children and adolescents from the boarding school of the town of Tashtagol and schoolchildren from the village of Krasnoye, Kemerovo Region. Excess radon levels in the air of living spaces and classes, a small excess of the maximum allowable concentration of gross forms of heavy metals in individual soil samples, and high toxic effects in the Drosophila gametes exposed to air samples were revealed in the Tashtagol children having higher genotoxic effects in the lymphocyte than those in the Krasnoye village ones. The findings suggest that the marked genotoxic effects recorded over a long time in the lymphocytes of children and adolescents living in Tashtagol may be associated with the complex influence of the above factors. It is north supplementing further investigations by an extended chemical analysis of water, air, snow, and soil samples taken in the places of residence and education of children.

[Genotoxic and cytotoxic effects in buccal cells of children living in ecologically different Kuzbass areas].

The article presents the results of the study of micronuclei and other types of cytogenetic aberrations in mucous tunic epithelium cells from children living in two different parts of the Kemerovo region (Tashtagol city, above-standard radon concentration exposition, n = 80), and Krasnoye settlement Leninsk-Kuznetsk area (comparison group, n = 41). The samples studied did not differ in the frequency of micronuclei containing cells. Tashtagol children sample showed significant increase in the number of binuclear cells, buccal epithelial cells with nuclear protrusions and with nuclear vacuoles, pyknotic cells, and apoptosis bodies. Reliable increase in average number of cells with chromatin condensation and kayolysis was found in the comparison group. It has been shown that the frequency of metaphase chromosome aberrations registered in peripheral blood lymphocytes corresponds to the amount of nuclear aberrations detected in buccal epithelium cells using micronuclei test.

[Genome sensitivity and genotoxic effects features in children-teenagers affected by radon radiation in living and educational environment].

The results of chromosomal aberration level and spectrum study in 48-hours peripheral blood lymphocytes cultures of 10-19 years old children-teenagers (n = 132, mean 14.2 +/- 0.16 years old) living in the south part of Kemerovskaya area Gornaya Shoria are presented. Mean metaphases with aberrations were 4.74 +/- 0.21% in studied group that is significantly higher (p < 0.01) than background level of this index in this region (Kemerovskaya area)- 2.62 +/- 0.29%. Aberrations frequencies of separate classes were 2.83 +/- 0.16 for single fragments; 1.89 +/- 0.14 for pair fragments; 0.05 +/- 0.02 for chromatide exchanges and 0.32 +/- 0.05 for chromosome type exchanges. Furthermore in 6 individuals (4.55%) were found Rogue cells that were contained polycentric, ring chromosomes and multiple pair dot fragments. The reasons of chromosomal aberrations frequency increasing in this mountain area inhabitants are discussed (ultrahigh radon radiation doses influence are included).

[Quantitative characteristics of chromosomal aberration frequency in the residents of the regions with different levels of cancer incidences].

We present the results of cytogenetic monitoring of the districts in Kemerovo region, which differ in standardized indices of cancer incidence. It has been shown that residents of the districts with high incidence of malignancies had higher average frequency of metaphases with chromosomal aberrations than the control group (4.06 +/- 0.12% and 2.76 +/- 0.13%, respectively). This difference is caused primarily by single or paired fragments. The increase in the frequency of aberrant metaphase incidence in the districts with elevated cancer frequency was observed both in the male and female groups as well as both in adults and children.

[Polymorphisms in glutathione S-transferase M1 and T1 (GSTM1 and GSTT1) in the indigenous and the nonresident population of the Kemerovo region].

GSTM1 and GSTT1 gene polymorphisms were studied in Shorians, Teleuts, and Caucasians of the Kemerovo region. It has been shown that distribution of homozygous deletions in the examined groups is significantly heterogeneous. The frequency of deletion genotypes and combinations of deletion in these genes was lower in Shorians and, Teleuts than in Caucasians.

[Cytogenetic analysis of genotoxic effects in subjects employed in heat power industry].

Chromosomal aberration rate has been estimated in peripheral blood lymphocytes of subjects occupationally exposed to a set of hazardous factors (employees of the Kemerovo Heat Power Plant). The frequency of metaphases with aberrations in the workers (3.23 +/- 0.26%, N = 104) is significantly higher than in control subjects (2.11 +/- 0.28%, N = 70). The cytogenetic aberrations did not depend on the sex, age, duration of employment, or smoking.

[A modification factor of spontaneous chromosomal aberrations in miner's towns and settlements].

The level and qualitative spectrum of spontaneous chromosomal aberrations (CA) were comparatively analyzed in the lymphocytes of 655 children and adolescents from the Kemerovo Region. The presented sample was divided into 3 groups according to the type of an inhabited locality: 1) small miner's towns; 2) large industrial towns; and 3) rural localities. The maximum frequency of CA (3.77 +/- 0.22%) was noted in a group of dwellers in the miner's towns; its minimum frequency (2.68 +/- 0.17%) among the rural inhabitants. The significant clastogenic effects (including the markers of radiation exposure) were detected in the miner's towns located in the southern part of the region, which represented mountain and submountain areas. At the same time, in the northern and western parts of the Kemerovo Region, the average frequencies of CA in children and adolescents did not exceed the control background values. Thus, the residence in the inhabited localities specializing in mining is not a factor of absolute toxicogenetic risk.

[Complex analysis of mutagenic and carcinogenic jeopardy of work conditions on JSC "Cox" in Kemerovo].

The authors present results of complex study concerning mutagenic and carcinogenic effects of work conditions in chemical-recovery industry. Oncologic morbidity and frequency of chromosomal aberrations in workers group is considerably higher than in controls. These effects appear to increase in males with longer length of service.

[Genomic dosages of active rRNA genes in coke-oven workers]. / genomnye dozy aktivnikh genov rRNK u rabochikh kaksokhimicheskogo proizvodstva.

Genomic dosage (copy number) of active ribosomal genes was evaluated using visual semi-quantitative method determining the sizes of Ag-NORs in acrocentric chromosomes after selective silver nitrate staining. A relationship between the length of service and the active ribosomal gene copy number was established: the highest numbers of active rRNA genes were observed in coke-oven workers with a length of service exceeding 20 years. An inverse relationship between the individual doses of active ribosomal genes and toxicogenetic susceptibility of the workers to the occupational factors was also revealed.

[Quantitative characteristics of the frequency of chromosomal aberrations in a group of residents of a large western Siberian industrial region]. / Kolichestvennye kharakteristiki chastoty khromosomnykh aberratsii v gruppe zhitelei krupnogo promyshlennogo regiona zapadnoi Sibiri.

The results of a 15-year study of chromosome aberration frequency in cultured peripheral blood lymphocytes from subjects living in the Kuzbass industrial region are presented. The database for the analysis of the main parameters of chromosome aberrations contains data on 925 subjects, with the total number of cells examined being 92,900. It has been found that the total frequency of aberrant metaphases in the database is 3.73 +/- 0.1%, whereas this frequency for the sample of subjects from industrial areas of this region (the basic control group) is significantly lower (2.86 +/- 0.26%). It has been demonstrated that the sex and age of the subjects do not affect substantially the frequency of any type of chromosome aberrations. Tobacco smoking is associated with a slight increase in chromosome damage frequency; however, the difference between smokers and nonsmokers is insignificant even among subjects exposed to occupational hazards. The possible causes that have determined the increased basic and background chromosome aberration frequencies in the population of the Kemerovo oblast compared to these parameters for the European part of Russia and the CIS are discussed.

[Comparative assessment of the clastogenic potential of various industrial enterprises]. / Sravnitel'naia otsenka klastogennogo potentsiala promyshlennykh predpriiatii raznogo profilia.

The paper comparatively assesses the level and qualitative spectrum of chromosomal aberrations (CA) in 192 workers engaged in 3 industries (cake and by-product, aluminum, and mining concentration processes). The maximum and minimum rates (6.43(+)-0.32% and 3.81(+)-0.46%) of CA have been observed in those engaged in cake and by-product and mining concentration processes, respectively. The combined influence of chemical and radiation factors are a cause of the higher rate of CA. Gender- and age-specific features do not effect on the level of structural CA. Smoking is a factor of their slight modification as there are no significant differences in the frequencies of aberrations between smokers and non-smokers in any professional group. There is an indirect relationship between the frequency of CA and the length of service, which may be different under the conditions of various industries.

[A study of the genetic basis of susceptibility to occupational fluorosis in aluminum industry workers of Siberia]. / Izuchenie nasledstvennykh osnov podverzhennosti professional'nomu fliuorozu rabochikh aliuminievykh zavodov Sibiri.

The phenotype frequency distributions of several classical blood genetic markers and dermatoglyphic characters were analyzed in workers of Siberian aluminum plants who had occupational fluorosis. Comparison with healthy workers revealed significant differences in frequencies of several markers. Phenotypes B (AB0), D (Rh), MN (MN), P1 (P), Le a (Lewis), Gc 2-1, Cx (on both hands), Th/I+ (on the left hand), C3, and C4 (HLA) were associated with higher risk of occupational fluorosis.