Проведен дескриптивный эпидемиологический анализ 104978 впервые выявленных случаев злокачественных новообра-зований (ЗНО) за 25-летний период наблюдения (1981-2005 гг.) среди населения Белгородской области, одной из 16 территорий Российской Федерации, загрязненных в результате аварии на Чернобыльской АЭС. Изучены возрастно-половые особенности формирования онкозаболеваемости на популяционном уровне в постчерно-быльский период. Показано, что воздействие малых доз об-лучения после чернобыльской аварии привело к перераспре-делению развития онкопатологии по годам жизни, причем в рамках популяционной предрасположенности развития ЗНО. Рост популяционной онкозаболеваемости в постчернобыльский период происходит за счет высокой заболеваемости лиц пожи-Ключевые слова: чернобыльская авария, малые дозы ра-диации, онкозаболеваемость, злокачественные новообразова-ния, постчернобыльский период, популяционная заболевае-мость, дескриптивный эпидемиологический анализ, Белго-родская область.

Descriptive epidemiological analysis of more than 200 thousands of new cancer cases over 25-year period (1981-2005) among population of the Belgorod and Bryansk Regions affected as a result of the Chernobyl accident was carried out. Age-gender dependencies of population oncopathology development during this period as well as the dynamics the incidence changes in separate nosological units were determined. It was shown that exposure in low dose after the Chernobyl accident led to wavy change of the incidence with the period 5-7 years and that radiation-induced incidence developed in the format of spontaneous one. The role of physiological factors of organism and processes of cell proliferation and differentiation in cancer development are discussed.

On the blood lymphocytes of prostate cancer (PCa) patients before and during radiotherapy: DNA damage by DNA commet assay (DNA double strand breaks - DSB); the frequency of cells with micronuclei (MN) with cytokinetic cytochalasin block; the adaptive response induction by the additional irradiation of PHA stimulated lymphocytes in the doses of 0.05 and 1.0 Gy 24 h and 48 h after stimulation were studied. Changes of these parameters with the decreasing of prostate specific antigen (PSA) have been compared. PSA decreasing is an adequate of the radiotherapy efficiency. It was shown that in oncological patients the DSB level and the frequency of cells with MN have been increased. During radiotherapy (in 3 months) the DNA DSB level and the frequency of cells with MN is enhancing. The degree and direction change of these parameters coincide. It was discovered the significant correlations between the enhancing of DNA DSB level and the cell frequency with MN during therapy and degree of the PSA level decreasing. Then it was shown that when the cell frequency with MN before treatment is higher the radiotherapy efficiency is worse. These results can have great significance for the evaluation of the prognosis of the treatment efficiency. The investigation of lymphocytes for the adaptive response ability has shown that in the patients with the pronounced adaptive response before radiotherapy the decrease of PSA level during treatment was not significant (in mean 3.5-3.6 ng/ml); when the adaptive response is absent or the phenomenon of enhanced radiosensitivity was observed the PSA level (in the most cases) was decreased very essential (in mean 0.07 ng/ml). We can suppose that prognosis of the treatment efficiency of the prostate cancer patients with the pronounced adaptive response in blood lymphocytes will be worse.

У лимфоцитов крови больных раком предстательной железы (РПЖ) до и во время лучевого лечения изучали: поврежденность ДНК методом ДНК-комет (двунитевые разрывы ДНК – ДР ДНК); частоту клеток с микроядрами (МЯ) при использовании цитокинетического блока цитохалазином В; индукцию адаптивного ответа при дополнительном облучении ФГА стимулированных лимфоцитов в дозах 0.05 и 1.0 Гр через 24 и 48 ч после стимуляции. Изменения этих показателей сравнивали со степенью снижения уровня простатспецифического антигена (ПСА), что является адекватным критерием эффективности лечения. Обнаружено, что в лимфоцитах онкологических больных повышен выход ДР разрывов ДНК и частота клеток с МЯ. При проведении лучевой терапии (в течение 3 мес) уровень ДР ДНК и частота клеток с МЯ возрастают. Степень и направленность изменения этих показателей совпадают. Были обнаружены достоверные корреляционные зависимости между степенью увеличения выхода ДР ДНК и частоты клеток с МЯ во время лечения и степенью снижения уровня ПСА. Показано, что чем выше исходная частота лимфоцитов с МЯ (до лечения), тем хуже эффективность лечения. Эти результаты могут иметь большое значение для определения прогноза эффективности лечения. Исследование способности лимфоцитов к индукции адаптивного ответа показало, что у больных с выраженным адаптивным ответом до лечения отмечается менее значительное снижение уровня ПСА во время лечения (в среднем до 3.5–3.6 нг/мл); при отсутствии адаптивного ответа или индукции повышенной радиочувствительности уровень ПСА в большинстве случаев снижается весьма существенно (в среднем до 0.07 нг/мл). Можно полагать, что прогноз эффективности лечения больных РПЖ с адаптивным ответом будет хуже.

Individual radiosensitivity of prostate malignant tumor cells were estimated in blood of 122 patients in accordance with the level of prostate-specific antigen. Estimation has been performed in dynamics (before and after 3, 6, 12, 18, 24, 30 and 36 months) after radiation (external beam radiotherapy with total dose 70 Gy, brachytherapy with clinical dose 140-170 Gy) and hormone-radiation therapy. It was detected the differences of prostate tumors in the radioresistance. Levels of antigen at all times of detection in patients with relative radioresistant tumors (39 patients) were higher then in patients with radiosensitive tumors (81 patients). The number of persons with clinically unfavorable clinical prognosis in the group of patients with relative radioresistant tumors were registered 2 times more often then in group with radiosensitive timorous (35.9% vs. 16.0%). The ratio of patients with radiosensitive and relative radioresistant tumors depends on the method of treatment. It is supposed that after neoadjuvant hormone therapy tumour becomes more radiosensitive.

Индивидуальная радиочувствительность злокачественной опухоли предстательной железы оценена в крови 122 больных по уровню простатического специфического антигена (ПСА) в динамике в течение 36 мес после лучевого (дистанционная лучевая терапия в суммарной очаговой дозе 70 Гр, брахитерапия в дозе 140–170 Гр) и гормонолучевого лечения. Опухоли предстательной железы различаются по степени радиочувствительности. Показатели ПСА на всех сроках обследования у больных с менее радиочувствительными опухолями (39 человек) достоверно выше, чем у больных с более радиочувствительными (81 человек). Число лиц с неблагоприятным прогнозом клинического течения заболевания в группе больных с менее радиочувствительными опухолями регистрируется в 2 раза чаще, чем с более радиочувствительными (35.9% против 16.0% соответственно). Радиочувствительность опухолей зависит от метода лечения. Делается предположение, что после неоадъювантной гормонотерапии опухоль становится наиболее радиочувствительной.

BACKGROUNDAfter the Chernobyl nuclear power plant accident in April 1986, a large increase in the incidence of childhood thyroid cancer was reported in contaminated areas. Most of the radiation exposure to the thyroid was from iodine isotopes, especially 131I. We carried out a population-based case-control study of thyroid cancer in Belarus and the Russian Federation to evaluate the risk of thyroid cancer after exposure to radioactive iodine in childhood and to investigate environmental and host factors that may modify this risk.METHODSWe studied 276 case patients with thyroid cancer through 1998 and 1300 matched control subjects, all aged younger than 15 years at the time of the accident. Individual doses were estimated for each subject based on their whereabouts and dietary habits at the time of the accident and in following days, weeks, and years; their likely stable iodine status at the time of the accident was also evaluated. Data were analyzed by conditional logistic regression using several different models. All statistical tests were two-sided.RESULTSA strong dose-response relationship was observed between radiation dose to the thyroid received in childhood and thyroid cancer risk (P<.001). For a dose of 1 Gy, the estimated odds ratio of thyroid cancer varied from 5.5 (95% confidence interval [CI] = 3.1 to 9.5) to 8.4 (95% CI = 4.1 to 17.3), depending on the risk model. A linear dose-response relationship was observed up to 1.5-2 Gy. The risk of radiation-related thyroid cancer was three times higher in iodine-deficient areas (relative risk [RR]= 3.2, 95% CI = 1.9 to 5.5) than elsewhere. Administration of potassium iodide as a dietary supplement reduced this risk of radiation-related thyroid cancer by a factor of 3 (RR = 0.34, 95% CI = 0.1 to 0.9, for consumption of potassium iodide versus no consumption).CONCLUSIONExposure to (131)I in childhood is associated with an increased risk of thyroid cancer. Both iodine deficiency and iodine supplementation appear to modify this risk. These results have important public health implications: stable iodine supplementation in iodine-deficient populations may substantially reduce the risk of thyroid cancer related to radioactive iodines in case of exposure to radioactive iodines in childhood that may occur after radiation accidents or during medical diagnostic and therapeutic procedures.

Results of the analysis of our own and literature data on the occurrence and development of radiation-induced thyroid cancer are presented. The analysis involved the distribution of the thyroid cancer incidence among 1 million children and 3 million adults, by age and sex, living in the radioactively contaminated territories of Russia; published data of the United Thyroid Cancer Registry of Russia and Byelorussia; results of medical examinations of the populations; and other information. Main attention was paid to the understanding of the latency period of spontaneous and radiation-induced cancers, comparison of oncopathology features in children and adults, and the role of screening in the increase of incidence rate parameters. The analysis permitted an offering of a new interpretation of several previously known facts and the developing of new explanations regarding the induction and development of radiogenic thyroid cancer, particularly regarding a far more significant increase of the thyroid cancer incidence in adults, living in the contaminated territories, than has been considered earlier.

Fine-needle aspiration biopsy of cervical lymph nodes was carried out in 22 patients with suspected metastatic involvement with medullary thyroid carcinoma (MTS). It was followed by cytopathological examination of aspirates and assay of of thyrocalcitonin (TCT) in fine-needle washings. TCT determinations proved highly informative as well as significantly high in all seven cases of MTS involvement (26-8,484.87 pg/ml, mean 2,208 +/- 1,722 pg/ml).

Acute 12-minute exposure of laboratory rats to microwaves with specific dose rate (SAR) of 30 W/kg that exceeded a basal metabolism caused a transient response of hyppophysis-thyroid system of compensatory-adaptive character. Prolonged exposure to microwaves of less intensity (SAR = 6 W/kg, which approximately corresponds to basic metabolic rate for these animals) caused insufficiency of the function of thyroid control in a form of primary hypothyroidis.

The collective influence of biologic, physical, and other factors that modify risks of radiation-induced cancer introduce uncertainties that limit precision of estimates of human cancer risk especially for low dose region. It can be easily demonstrated in reviewing an increased incidence of thyroid cancer in children affected as a result of the Chernobyl accident. While the number of cancers is extremely high in relative figures, it is rather low in absolute value. If one try to analyse the occurrence of excessive cancers in children in dependence of age, sex and other factors the results lose statistical significance. On the basis of our 12-year's experience in dealing with this problem[4, 6, 8 ], we offered a functional mechanistic model of thyroid pathology development in the post-Chernobyl period. The model highlights the tight correlation between the response of thyroid gland at the action of ionizing radiation and its functional state. The model takes into account that the functional state of thyroid - its volume, iodine intake, production of hormones, etc. - has an influence upon the formation of the absorbed dose, mainly due to radioactive iodine, as well as on the type and level of radiation response manifestation. The functional activity of the gland depends both on peculiarities of pubescent period in boys and girls, on periods of pregnancy, lactation and menopause in women and on the external factors (iodine endemy in the environment or iodine prophylaxis). This permits to consider and analyse a wide set of thyroid disorders possibly related to radiation exposure.

В то же время полученные результаты не могут быть объяснены прямой зависимостью доза — эффект и требуется дополнительная работа по выделению всех возможных моделирующих факторов для разработки программ эффективного мониторинга и возможных профилактических мероприятий. The incidence of thyroid cancer in subjects exposed to radiation in childhood increased in the Bryansk, Kaluga, Tula and Orel regions of the Russian Federation which were exposed to the highest doses as a result of the Chernobyl accident. Retrospective and prospective verification of diagnoses of thyroid cancer is needed for obtaining quantitative characteristics of increases in the relative and absolute risk of the disease. Epidemiological analysis of verified cases of thyroid cancer in the Bryansk region showed that the relative risk of thyroid cancer increased in 1986-1997 at both exposed and relatively pure territories: 8.13 and 1.78, respectively (p<0.05). The relative risk is the highest in the group aged 0-4 years at the moment of the accident: 67.74 and 4.72, respectively (p<0.05). On the other hand, these results cannot be explained by the direct dose-effect relationship, and further studies are needed to distinguish all probable modulating factors, in order to develop programs of effective monitoring and prophylactic measures.