Vol 29, No 3 (2022)

The second part of the review considers the following three main areas of research on the toxicity of nanoparticles (NPs): environmental toxicity, molecular mechanisms of toxicity, and reproductive toxicity. The studies carried out on aquatic and soil model organisms are described, with consideration of the effects of NPs in concentrations close to natural in water with different salinity, as well as in comparison with the effects of ions. The articles devoted to various aspects of NP-induced oxidative stress are listed, the estimations of genotoxicity and mutagenicity of NPs using different standard methods are described, and the currently known data on the formation of protein crowns around NPs are considered. Questions are stated about the dose-dependence of effects and the influence of the applied stabilizing coating. The influence of NPs on the prenatal and postnatal development of various model vertebrate species is considered, which includes morphological disturbances, changes in gene expression and in the behavior of grown animals, as well as the influence on the reproductive system in adult females and males. The main methods for the quantitative measurements of the content of NPs in biological samples are also considered as the necessary stage of research on the toxicity of NPs for humans and animals.

BACKGROUND: In the area of physiology and medicine, special emphasis is placed on the study of hypoxic conditions. Hypoxic responses of some major physiological systems, including blood circulation, are described. However, the cardiological component of these individual responses, and their variability at different levels of acute hypoxia (AH) remains a poorly-studied aspect.

AIM: To study the individual characteristics of the response types in conjugated ECG parameters, and their variations at different stages of mild and medium AH.

MATERIAL AND METHODS: The experiments were performed on male subjects (18–26 years old) divided into two groups (n₁=30 and n₂=29), who were exposed to AH of 14.5% at 12.3% O₂ for 20 min. Amplitude (P₁II, RII, T₁II, BA_L, BA_R) and temporal (R–R, Q–T) ECG parameters, and blood oxygenation (SpO₂) were determined at AH periods (at 5, 10, and 20 min respectively). In subgroups (clusters), the features of types with “low” and “high” responses, and their stability in AH are described.

RESULTS: Clustering of ECG variations with AH of 14.5% and 12.3% O₂ identified two subgroups (clusters), that differed at least in the magnitude of the decrease in the total BA_L and R–R. With AH of 14.5% O₂, the number of different ECG parameters between subgroups gradually increased: at 5 min — BA_L (p <0.001), at 20 min — RII (p=0.047), T₁II (p=0.016), BA_L (p <0.001), R–R (p=0.035), Q–T (p=0.008), and with AH 12.3% O₂ — only BA_L (p <0.001). It was found that at all periods of AH of 14.5% O_2, in 60% of individuals, the type of response remained. Regarding AH of 12.3% O₂ — in 55.2% of the other cases, the type of response of ECG parameters changed. At the same time, no parallels were observed between the types of reactions and deviations in SрO₂.

CONCLUSION: From this study, It can be assumed that there are two types of conjugated reactions of ECG parameters in response to mild and medium AH, and their variability is absent in 40% and 44.8% of cases, respectively, as well as the independence of differentiation of ECG responses types from hypoxemia.

AIM: To study the state of the genome by indicators of retrotransposon activity — the gene encoding DNA methyltransferase 1 (DNMT1); DNA damage in animals from the natural population of the bank vole (Clethrionomys glareolus) living in the vicinity of a preserved landfill contaminated with low concentrations of dioxins (landfill of production and consumption waste — "Salariyevo", Moscow).

MATERIAL AND METHODS: The activity of ERV-L, B1, and L1 retrotransposons and the transcription level of the DNMT1 gene were evaluated by real-time PCR. The stability of DNA in liver and bone marrow cells was characterized by the comet assay method. Afterward, the obtained characteristics of the state (stability, reactivity, and damage) of the genome in response to environmental stress factors were compared in groups of animals from the study and conditionally control samples.

RESULTS: The effects of a decrease in the activity of retrotransposons of classes B1 and L1, and an increase in DNMT1 gene expression level were revealed in voles from the natural population living under the long-term chronic exposure to low doses of dioxins decrease in the activity of retrotransposons of classes B1 and L1, and an increase in the expression level of the DNMT1 gene were revealed. An increased level of DNA damage (on average up to 56% of the DNA in the tail of the comet) was detected in hepatocytes, with the addition of winter environmental factors to the chronic effect of small subtoxic doses of dioxins.

CONCLUSION: Suppression of retrotransposon activity and increased expression of its epigenetic regulator (DNMT1) are regarded as adaptive responses to long-term chronic exposure to low doses of dioxins polluting the environment. The alteration in the reactivity and destabilization of the genome indicates the launch of the initial mechanisms of the toxic process formation. The created and tested methodological base for its study opens up prospects for establishing a threshold level, and as a result, substantiating indicators for screening assessment of local (territorial) risk to public health by biomonitoring.