MORPHOLOGICAL TRAITS OF HEPATIC PARENCHYMAL TISSUE REPAIR FOLLOWING EXPERIMENTAL INJURY.

The aim of the study was to investigate morphological traits of hepatic parenchymal tissue repair in response to injury using the conventional technique (closure) and an innovation method (such as hemostatic medication swab packing and modified batching). The experimental study was carried out on laboratory rats of the Winzar breed using light microscopy, standard stains for micropreparations, and morphometry. Histopathologic examination of micropreparations stained by standard methods revealed pronounced dystrophic processes in hepatocytes located near the necrotic zone (albuminous and hydropic degeneration and chromatin fragmentation in the nuclei). Morphometric studies showed a significant decrease (p<0.001) in almost all indicators of the size of cells and nuclei both near necrosis and distant from it on day 28 of the experiment in the experimental group in comparison to the control group. The results obtained pointed to more intense repair processes when applying the innovation method.

Cervical and Endometrial Cancer Incidence in the Female Population from the Bryansk Region Living in Conditions of Chemical, Radioactive and Combined Environmental Contamination (2000-2020).

At the end of 36 years after the Chernobyl disaster, about 5 million people still live in the radioactively contaminated territories of Russia, Ukraine, and Belarus, and the density of radioactive contamination by Cesium-137 and Strontium-90 will remain radiologically significant for decades. We assessed cervical and endometrial cancer primary incidence (new cases) in the female population from the Bryansk region living in conditions of chemical, radioactive, and combined environmental contamination for 2000−2020. We found a significant increase in the long-term trend in the primary incidence of cervical and endometrial cancer in all the studied groups, regardless of the environmental conditions of residence (p < 0.00001). We did not find statistically significant differences in the incidence of cervical and endometrial cancer in women, regardless of the level of chemical, radioactive, and combined environmental contamination. However, women living in environmentally unfavorable areas (in total, in the territories of chemical, radioactive, and combined contamination) are statistically significantly more likely to develop endometrial cancer in terms of relative risk compared to environmentally safe (control) areas (RR 1.17 (1.08−1.27)). No such pattern was found for cervix cancer. It should be noted, since environmentally safe (control) areas have a certain level of contamination (albeit low), RR is underestimated.

Ovarian Malignancies Frequency in the Female Population from the Bryansk Region Living in Conditions of Radioactive, Chemical and Combine Contamination (2000-2020).

Background: Radioactive contamination and chemical pollution of the environment can affect the processes of carcinogenesis, including the formation of malignant neoplasms of the ovaries in women. We used the data of official state statistics for 2000-2020 to test the hypothesis about the effect of radioactive contamination (following the Chernobyl disaster) and chemical pollutants on the incidence of ovarian malignancies in the female population of the Bryansk region. Methods: A variety of statistical approaches were used to estimate the incidence of ovarian malignancies, including the Shapiro-Wilk test, Mann-Whitney U test, Spearman's rank correlation test and linear regression. Results: We did not establish statistically significant differences in the frequency of primary morbidity of women with malignant neoplasms of the ovaries, regardless of the environmental conditions of living. Furthermore, no significant correlations were found between the frequency of primary morbidity of ovarian malignancies, both with the level of contamination by Cesium-137 and Strontium-90, and air pollution with volatile organic compounds, carbon monoxide, sulfur dioxide and nitrogen oxides. A statistically significant increase in the long-term trend in the frequency of ovarian malignant neoplasms was revealed in the areas of chemical pollution (p = 0.02), however, in other territories, no statistically significant regularities were established. The forecast of the frequency of newly diagnosed malignant neoplasms of the ovaries on average in the Bryansk region shows an increase of 12.4% in 2020 in comparison with the real data for 2020, while the largest increase in predicted values is recorded in the territories of radioactive contamination (by 79.6%), and the least in the combined territories (by 6.9%). Conclusions: The results obtained indicate the need for further work to understand the trends in the presence/absence of independent and combined effects of pollutants and the growth of oncogynecological pathology from the perspective of assessing the distant and regional metastasis, histological and immunohistochemical profile of a specific malignant ovarian neoplasm with levels of environmental contamination.

Female breast cancer risk in Bryansk Oblast, Russia, following prolonged low dose rate exposure to radiation from the Chernobyl power station accident.

BACKGROUND: Ionizing radiation is a known cause of female breast cancer, but there have been few studies of the risk after prolonged radiation exposure at low dose rates. METHODS: This population-based case-control study estimated breast cancer risk after ∼25 years' exposure to radiation from the Chernobyl accident. Cases (n = 468) were women ≤55 years old when first diagnosed with invasive breast cancer during October 2008 through February 2013, who lived in Bryansk Oblast, Russia at the time of the accident and their diagnoses. Controls, individually matched to cases on birth year, administrative district of residence and urban vs non-urban settlement during the accident, were women without breast cancer who lived in Bryansk Oblast at the time of the accident and on their cases' diagnosis dates (n = 468). Subjects were interviewed regarding residence, dietary and food source histories to support individualized estimation of their radiation doses to the breast, which ranged from 0.04 - 41 centigray (cGy) (mean 1.3 cGy). RESULTS: In multivariable analyses, the odds ratio for breast cancer risk was 3.0 [95% confidence interval (CI): 1.3, 7.0] and 2.7 (95% CI: 1.0, 7.3) in the seventh and eighth dose octiles, respectively, relative to the lowest octile. Analyses of dose effect modification suggested that radiation-related risk may have been higher in women who were younger at the time of the accident and/or at the time of diagnosis. CONCLUSIONS: This study suggests that prolonged exposure to ionizing radiation at low dose rates can increase risk of breast cancer.

ret/PTC activation is not associated with individual radiation dose estimates in a pilot study of neoplastic thyroid nodules arising in Russian children and adults exposed to Chernobyl fallout.

BACKGROUND: Ionizing radiation is the strongest risk factor known for the development of thyroid neoplasia. While previous studies have demonstrated a high prevalence of ret/papillary thyroid cancer (PTC) activation in cohorts of patients developing thyroid nodules after childhood exposure to ionizing radiation, no study has directly compared ret/PTC activation with individual estimates of radiation dose to the thyroid. This study combines individual thyroid dosimetry data with molecular analysis of surgically removed thyroid nodules in order to determine if ret/PTC activation in thyroid nodules is associated with increasing estimated radiation dose from Chernobyl. METHODS: This pilot study included adults and children diagnosed with PTC (n = 76) and children diagnosed with follicular adenomas (n = 24) during May 1986 through December 1999, who were living in the Bryansk Oblast of the Russian Federation at the time of the Chernobyl accident, who had paraffin-embedded thyroid surgical samples available and for whom an individual dose to the thyroid could be estimated. The frequency of ret/PTC activation was determined using RT-PCR analysis. Individual radiation doses to the thyroid were estimated using a semiempirical model, and data were collected by detailed interview, primarily of the participant's mother. RESULTS: ret/PTC oncogene activation was detected in 23.8% (5/21) and 14.5% (8/55) of the childhood and adult PTC cases, respectively, and 8.3% (2/24) of the follicular adenoma cases. No statistically significant differences were noted in age at the time of exposure or diagnosis, gender, latency period, or estimated radiation dose between PTC patients with or without ret/PTC activation. Further, no significant dose-response relationship was detected among PTC patients with ret/PTC activation. CONCLUSIONS: Factors other than individual thyroid radiation doses may influence the development and subsequent detection of ret/PTC oncogene activation in radiation related PTC arising in the Bryansk Oblast of the Russian Federation in the aftermath of the Chernobyl accident.

Childhood thyroid cancer, radiation dose from Chernobyl, and dose uncertainties in Bryansk Oblast, Russia: a population-based case-control study.

A population-based case-control study was conducted to estimate the radiation-related risk of thyroid cancer in persons who were exposed in childhood to (131)I from the Chernobyl accident of April 26, 1986 and to investigate the impact of uncertainties in individual dose estimates. Included were all 66 confirmed cases of primary thyroid cancer diagnosed from April 26, 1986 through September 1998 in residents of Bryansk Oblast, Russia, who were 0-19 years old at the time of the accident, along with two individually matched controls for each case. Thyroid radiation doses, estimated using a semi-empirical model based on environmental contamination data and individual characteristics, ranged from 0.00014 Gy to 2.73 Gy and had large uncertainties (median geometric standard deviation 2.2). The estimated excess relative risk (ERR) associated with radiation exposure, 48.7/Gy, was significantly greater than 0 (P = 0.00013) but had an extremely wide 95% confidence interval (4.8 to 1151/Gy). Adjusting for dose uncertainty nearly tripled the ERR to 138/Gy, although this was likely an overestimate due to limitations in the modeling of dose uncertainties. The radiation-related excess risk observed in this study is quite large, especially if the uncertainty of dose estimation is taken into account, but is not inconsistent with estimates previously reported for risk after (131)I exposure or acute irradiation from external sources.

Microarray comparative genomic hybridization reveals genome-wide patterns of DNA gains and losses in post-Chernobyl thyroid cancer.

Genetic gains and losses resulting from DNA strand breakage by ionizing radiation have been demonstrated in vitro and suspected in radiation-associated thyroid cancer. We hypothesized that copy number deviations might be more prevalent, and/or occur in genomic patterns, in tumors associated with presumptive DNA strand breakage from radiation exposure than in their spontaneous counterparts. We used cDNA microarray-based comparative genome hybridization to obtain genome-wide, high-resolution copy number profiles at 14,573 genomic loci in 23 post-Chernobyl and 20 spontaneous thyroid cancers. The prevalence of DNA gains in tumors from cases in exposed individuals was two- to fourfold higher than for cases in unexposed individuals and up to 10-fold higher for the subset of recurrent gains. DNA losses for all cases were low and more prevalent in spontaneous cases. We identified unique patterns of copy variation (mostly gains) that depended on a history of radiation exposure. Exposed cases, especially the young, harbored more recurrent gains that covered more of the genome. The largest regions, spanning 1.2 to 4.9 Mbp, were located at 1p36.32-.33, 2p23.2-.3, 3p21.1-.31, 6p22.1-.2, 7q36.1, 8q24.3, 9q34.11, 9q34.3, 11p15.5, 11q13.2-12.3, 14q32.33, 16p13.3, 16p11.2, 16q21-q12.2, 17q25.1, 19p13.31-qter, 22q11.21 and 22q13.2. Copy number changes, particularly gains, in post-Chernobyl thyroid cancer are influenced by radiation exposure and age at exposure, in addition to the neoplastic process.

Risk of thyroid cancer in the Bryansk Oblast of the Russian Federation after the Chernobyl Power Station accident.

This population-based case-control study investigated whether exposure to radiation from the Chernobyl Power Station accident is associated with an increased risk of thyroid cancer in children and adolescents aged 0-19 years at the time of the accident who were residing in the more highly contaminated areas of the Bryansk Oblast. Cases were diagnosed with thyroid cancer before October 1, 1997 (n = 26); two controls per case were identified from the Russian State Medical Dosimetrical Registry and were matched by gender, birth year, and raion of residence and type of settlement (urban, town, rural) on April 26, 1986 (n = 52). Individual radiation doses to the thyroid were estimated using a semi-empirical model and data were collected in interviews, primarily of the participants' mothers. Based on a loglinear dose-response model treating estimated dose as a continuous variable, the trend of increasing risk with increasing dose was statistically significant (one-sided P = 0.009). These data suggest that exposure to radiation from Chernobyl is associated with an increased risk of thyroid cancer, and that the relationship is dependent on dose. These findings are consistent with descriptive reports from contaminated areas of Ukraine and Belarus, and the quantitative estimate of thyroid cancer risk is generally consistent with estimates from other radiation-exposed populations.