Thyroid dose and thyroid cancer incidence after the Chernobyl accident: assessments for the Zhytomyr region (Ukraine)

In the Zhytomyr region, about 52 000 measurements of the ¹³¹I activity in thyroids were performed. On the basis of these measurements, individual doses have been assessed for the people monitored and age-dependent average doses have been estimated for those settlements with more than 11 direct measurements. In order to estimate the pattern of thyroid exposure in the Zhytomyr region, these doses have been interpolated or extrapolated to population groups who were not monitored during May–June 1986. For this purpose, a model has been developed based on a correlation between thyroid dose estimates with the ¹³⁷Cs deposition and the co-ordinates of the settlements relative to Chernobyl. Collective doses of people who were born in the years 1968 to 1986 were calculated. The radiation-induced thyroid cancer incidence in the period 1991 to 1995 was assessed by subtracting the spontaneous incidence from the observed incidence. The result is considerably lower than that observed in longer periods after external exposures. Possible reasons for this difference are discussed. Received: 17 January 1997 / Accepted in revised form: 2 October 1997     

Induction of chromosome aberrations and micronuclei in human peripheral blood lymphocytes at low dose of radiation

The chromosome damage induced by the doses of y-irradiation 6)Co in peripheral blood lymphocytes was studied using different cytogenetic assays. Isolated lymphocytes were exposed to 0.01-1.0 Gy, stimulated by PHA, and analysed for chromosome aberrations at 48 h postirradiation by metaphase method, at 49 h--by the anaphase method, at 58 h by micronucleus assay with cytochalasin B and, additionally, micronuclei were counted at 48 h on the slides prepared for the metaphase analysis without cytochalasin B. Despite of the quantitative differences in the amount of chromosome damage revealed by different methods all of them demonstrated complex nonlinear dose dependence of the frequency of aberrant cells and aberrations. At the dose range from 0.01 Gy to 0.05-0.07 Gy the cells had the highest radiosensitivity mainly due to chromatid-type aberration induction. With dose increasing the frequency of the aberrant cells and aberrations decreased significantly (in some cases to the control level). At the doses up to 0.5-0.7 Gy the dose-effect curves have become linear with the decreased slope compare to initial one (by factor of 5 to 10 for different criteria) reflecting the higher radioresistance of cells. These data confirm the idea that the direct linear extrapolation of high dose effect to low dose range--the procedure routinelly used to estimate genetic risk of low dose irradiation--cannot be effective and may lead to underestimation of chromosome damage produced by low radiation doses. Preferences and disadvantages of used cytogenetic assays and possible mechanisms of low ionising radiation doses action were discussed.     

Thyroid dose reconstruction for the population of Belarus after the Chernobyl accident

An ¹³¹I environmental transfer model – adapted for Belorussian conditions – was applied to estimate thyroid doses for different population groups. For this purpose the available data were analysed and the important radioecological parameters assessed, i.e. (a) the elimination rate of ¹³¹I from grass due to weathering and growth dilution, (b) the initial interception of ¹³¹I by vegetation, (c) the transfer coefficient for ¹³¹I from grass to cow's milk, (d) the yield of pasture grass and (e) the milk consumption rate. Additionally, the influence of applied countermeasures has been taken into account, such as the interruption of locally produced milk consumption, and the appropriate correction factors have been estimated. As a result, the average age-dependent thyroid doses were assessed for the Belorussian population. The highest average doses in children (> 1 Gy) have been estimated for the Bragin, Khoiniki, Narovlia and Vetka raions of the Gomel oblast. The thyroid exposure tends to decrease from the southeastern (closest to the Chernobyl nuclear power plant areas) to the northwestern part of the republic. When comparing the assessed thyroid doses with dose estimates derived from direct ¹³¹I activity measurements in thyroids (for the locations with more than 15 direct measurements), the results agree fairly well. The model calculation may perhaps overestimate thyroid doses of the population residing in the settlements of the central and northern parts of Belarus, distant from the areas with direct measurements of ¹³¹I activities in soil, grass and milk. These thyroid dose estimates may serve as a basis for further epidemiological studies and risk analyses.     

Biological dosimetry for astronauts: a real challenge

Manned space missions recently increased in number and duration, thus it became important to estimate the biological risks encountered by astronauts. They are exposed to cosmic and galactic rays, a complex mixture of different radiations. In addition to the measurements realized by physical dosimeters, it becomes essential to estimate real biologically effective doses and compare them to physical doses. Biological dosimetry of radiation exposures has been widely performed using cytogenetic analysis of chromosomes. This approach has been used for many years in order to estimate absorbed doses in accidental or chronic overexposures of humans. In addition to conventional techniques (Giemsa or FPG staining, R- or G-banding), faster and accurate means of analysis have been developed (fluorescence in situ hybridization [FISH] painting). As results accumulate, it appears that strong interindividual variability exists in the basal level of aberrations. Moreover, some aberrations such as translocations exhibit a high background level. Radiation exposures seem to induce variability between individual responses. Its extent strongly differs with the mode of exposure, the doses delivered, the kind of radiation, and the cytogenetic method used. This paper aims to review the factors that may influence the reliability of cytogenetic dosimetry. The emphasis is on the exposure to high linear energy transfer (LET) particles in space as recent studies demonstrated interindividual variations in doses estimated from aberration analysis after long-term space missions. In addition to the problem of dose estimates, the heterogeneity of cosmic radiation raises questions relating to the real numbers of damaged cells in an individual, and potential long-term risks. Actually, densely ionizing particles are extremely potent to induce late chromosomal instability, and again, interindividual variability exists in the expression of damage.     

Native American Exposure to 131Iodine from Nuclear Weapons Testing in Nevada

A great deal of work has been done to reconstruct doses from Nevada Test Site fallout, yet the unique exposures of Native American communities continue to be neglected. It is possible to estimate the exposures of these communities through a process of collaborative information gathering and analysis. This article builds on a previous exercise that demonstrated the substantial doses received through the consumption of contaminated game. The updated model includes new information on the deposition of ¹³¹iodine, an assessment of the neonatal thyroid doses received through breast milk, an exploration of the effect of population mobility on dose estimates, and estimates of thyroid cancer risk. All thyroid dose estimates from the rabbit exposure pathway are comparable in magnitude to National Cancer Institute comprehensive dose estimates that assume exposure to contaminated milk from backyard cows and goats. Dose estimates from the rabbit exposure pathway are larger than estimated doses from store-bought milk by an average factor of six. Taking historical population mobility patterns into account may result in slightly lower estimates of dose. The quantification of this exposure pathway is considered be an advance toward a more appropriate dose reconstruction for communities with diets high in wild game.     

Thyroid doses in Ukraine due to 131I intake after the Chornobyl accident. Report II: dose estimates for the Ukrainian population

This paper describes the revision of the thyroid dosimetry system in Ukraine using new, recently available data on (i) revised ¹³¹I thyroid activities derived from direct thyroid measurements done in May and June 1986 in 146,425 individuals; (ii) revised estimates of ¹³¹I ground deposition density in each Ukrainian settlement; and (iii) estimates of age- and gender-specific thyroid masses for the Ukrainian population. The revised dosimetry system estimates the thyroid doses for the residents of the settlements divided into three levels depending on the availability of measurements of ¹³¹I thyroid activity among their residents. Thyroid doses due to ¹³¹I intake were estimated in this study for different age and gender groups of residents of 30,353 settlements in 24 oblasts of Ukraine, Autonomous Republic Krym, and cities of Kyiv and Sevastopol. Among them, dose estimates for 835 settlements were based on ¹³¹I thyroid activities measured in more than ten residents (the first level), for 690 settlements based on such measurements done in neighboring settlements (the second level), and for 28,828 settlements based on a purely empirical relationship between the thyroid doses due to ¹³¹I intake and the cumulative ¹³¹I ground deposition densities in settlements (the third level). The arithmetic mean of the thyroid doses due to ¹³¹I intake among 146,425 measured individuals was 0.23 Gy (median of 0.094 Gy); about 99.8% of them received doses less than 5 Gy. The highest oblast-average population-weighted thyroid doses were estimated for residents of Chernihiv (0.15 Gy for arithmetic mean and 0.060 Gy for geometric mean), Kyiv (0.13 and 0.051 Gy) and Zhytomyr (0.12 and 0.049 Gy) Oblasts followed by Rivne (0.10 and 0.039 Gy) and Cherkasy (0.088 and 0.032 Gy) Oblasts, and Kyiv City (0.076 and 0.031 Gy). The geometric mean of thyroid doses estimated in this study for the entire Ukraine essentially did not change in comparison with a previous estimate, 0.020 vs. 0.021 Gy, respectively. The ratio of geometric mean of oblast-specific thyroid doses estimated in the present study to previously calculated doses varied from 0.51 to 3.9. The highest increase in thyroid doses was found in areas remote from the Chornobyl nuclear power plant with a low level of radioactive contamination: by 3.9 times for Zakarpatska Oblast, 3.5 times for Luhansk Oblasts and 2.9 times for Ivano-Frankivsk Oblast. The developed thyroid dosimetry system is being used to revise the thyroid doses due to ¹³¹I intake for the individuals of post-Chornobyl radiation epidemiological studies: the Ukrainian-American cohort of individuals exposed during childhood and adolescence, the Ukrainian in utero cohort, and the Chornobyl Tissue Bank.

     

Biological consequences of irradiation by low doses of technetium 99m: ultrastructural studies, p53 protein expression and cytogenetic effects.

Few studies concerning the potential genetic effects of diagnostic radionuclides used in nuclear medicine have been reported. The aim of this study was to evaluate the biological and cytogenetic consequences of two technetium 99m-labelled radiopharmaceuticals. Ultrastructural modifications of pulmonary cells were first investigated after injection of 99mTc labelled microspheres in the rat. On the same irradiated cells, nuclear expression of p53 protein was assessed using immunohistochemistry. Despite very high previously calculated doses delivered to pulmonary cells, no morpholological cell damage and no significant increase of nuclear expression of the p53 were noted. There was no correlation between the calculated dose and the ultrastructural biological damage. Secondly, a specific in vitro curve, activity/number of unstable chromosomal aberrations, corresponding to physical characteristics of 99mTc, was established to verify the potentiality of 99mTc to induce such aberrations. In vivo, cytogenetic effects were assessed on blood samples of 5 patients with various arthrosic and periarthrosic diseases obtained after bone scintigraphy. Aberration frequencies of both in vitro and in vivo irradiated lymphocytes were determined using the classical Fluorescence Plus Giemsa technique. No cytogenetic effects appeared with the routinely 99mTc injected activities as predicted by the in vitro curve.     

Cytogenetic biodosimetry and dose-rate effect after radioiodine therapy for thyroid cancer

This study set out to investigate chromosomal damage in peripheral blood lymphocytes of thyroid cancer patients receiving ¹³¹I for thyroid remnant ablation or treatment of metastatic disease. The observed chromosomal damage was further converted to the estimates of whole-body dose to project the adverse side effects. Chromosomal aberration analysis was performed in 24 patients treated for the first time or after multiple courses. Blood samples were collected before treatment and 3 or 4 days after administration of 2–4 GBq of ¹³¹I. Both conventional cytogenetic and chromosome 2, 4 and 12 painting assays were used. To account for dose-rate effect, a dose-protraction factor was applied to calculate the whole-body dose. The mean dose was 0.62 Gy (95% CI: 0.44–0.77 Gy) in the subgroup of patients treated one time and 0.67 Gy (95% CI: 0.03–1.00 Gy) in re-treated patients. These dose estimates are about 1.7-fold higher than those disregarding the effect of exposure duration. In re-treated patients, the neglected dose-rate effect can result in underestimation of the cumulative whole-body dose by the factor ranging from 2.6 to 6.8. Elevated frequency of chromosomal aberrations observed in re-treated patients before radioiodine therapy allows estimation of a cumulative dose received from all previous treatments.     

Stable and unstable chromosome aberrations in humans and other mammals in relation to the problems of biological dosimetry

Literature data of long-term cytogenetic follow-up of people exposed to radiation as a results of different radiation accidents are considered for the purpose of discussing of some problems of biological dosimetry. The results obtained for mammals are also presented. Of particular interest is a decrease in the level of dicentrics and symmetrical translocations in peripheral blood lymphocytes with the time after acute exposure depending on the dose of irradiation. The frequency of dicentrics decreases in accordance to the exponential law passing the fast and slow phases of elimination. In different radiation situations the values of the parameter which defines the half-life period of lymphocytes characterizing 50% reduction of cells with dicentrics markedly vary. However a general regularity is a decrease in the parameter value as the exposure dose increases. The level of stable translocations estimates by the EISH method remains relatively constant at doses below 1-2 Gy. At higher doses their level in peripheral blood lymphocytes declines with time due to which the retrospective dose appears to be underestimated. The reasons of such regularity, the role of various factors affecting the scoring of translocations, criteria of analysis of the given chromosome aberrations are discussed in the context of common agreements between leading European laboratories on the use of FISH for improving biological dosimetric estimates.     

Space radiation does not induce a significant increase of intrachromosomal exchanges in astronauts’ lymphocytes

Chromosome aberration analysis in astronauts has been used to provide direct, biologically motivated estimates of equivalent doses and risk associated to cosmic radiation exposure during space flight. However, the past studies concentrated on measurements of dicentrics and translocations, while chromosome intrachanges (inversions) have never been measured in astronauts’ samples. Recent data reported in the literature suggest that densely ionizing radiation can induce a large fraction of intrachanges, thus leading to the suspicion that interchanges grossly underestimate the cosmic radiation-induced cytogenetic damage in astronauts. We have analyzed peripheral blood lymphocytes from 11 astronauts involved in short- or long-term space flights in low-Earth orbit using high-resolution multicolor banding to assess the frequency of intrachromosomal exchanges in both pre- and post-flight samples. We did not detect any inversions in chromosome 5 from a total of 2800 cells in astronauts’ blood. In addition, no complex type exchanges were found in a total of 3590 astronauts’ lymphocytes analyzed by multifluor fluorescence in situ hybridisation. We conclude that, within the statistical power of this study, the analysis of interchanges for biological dosimetry in astronauts does not significantly underestimate the space radiation-induced cytogenetic damage, and complex-type exchanges or intrachanges have limited practical use for biodosimetry at very low doses.     

Results of dynamic cytogenetic study of children and teenagers living in areas, radioactive by contaminated after the Chernobyl accident

Results of multiyear cytogenetic study of children and teenagers living in areas, radioactive by contaminated after Chernobyl accident, were adduced. Mean density of 137Cs contamination in two compared living areas were 111 and 200 kBq/m2 and mean external doses accumulated for 1986-2001 were 6.7 and 11.4 mGy correspondingly. Averaged thyroid doses receives by subjects of all age groups in the second area were approximately 1.5 times higher than in the first area; in the youngest group (0-1 year) the doses were 114.3 and 174.3 mGy. During 17 years cytogenetic investigation approximately from 30% to 60% of examined persons were observed the increased level of chromosome aberrations in lymphocytes of peripheral blood. Average frequency of unstable aberrations (acentrics, dicentrics and centric rings) constituted about 0.4 per 100 cells (0.22 per 100 cells in controls) during all period of observation. Level of marker aberrations (dicentrics and centric rings) was increased almost all times of study and varied within 0.04-0.19 per 100 cell (0.03 in control group). The parallel investigation of frequency of stable aberrations by FISH method showed up their level about 3 times exceeding observed dicentrics level. Comparably higher indexes of cytogenetic disturbances were revealed in group exposed in utero during period of accident.     

An assessment of the radiological impact of the Windscale reactor fire, October 1957

On the 10th and 11 October 1957 a fire in the No 1 Pile at the Windscale establishment in Cumbria led to an uncontrolled release of activity to the atmosphere. The resultant cloud subsequently dispersed and radionuclides could be detected over England, Wales and parts of northern Europe. The extensive environmental measurements which were made during and after the release enabled a fairly accurate estimate to be made of the radiation doses to the most exposed individuals in the local population. Until recently, no estimates of the population dose resulting from the release had been published. This paper describes assessments which have been made by the NRPB of the population or collective dose from the release and of the possible associated health impact. In addition to the fission products that escaped, radionuclides were released from materials undergoing irradiation in the pile at the time of the fire. The assessment has included the results of a review of previously unpublished data which established the quantity of these nuclides released and considers their impact on both individual and population doses. The collective effective dose equivalent commitment from the release is estimated to have been 2.0 x 10(3) man Sv. The route of exposure which contributed the most to the collective dose was the inhalation pathway. Iodine-131 was the most important radionuclide, contributing nearly all of the collective dose to the thyroid and a large part of the collective effective dose. Polonium-210 and caesium-137 also made significant contributions; that from caesium-137 came in the longer term via external irradiation from ground deposits and the ingestion of contaminated foodstuffs. The methodology used in the study has been validated to a certain degree by comparing the predicted levels of individual thyroid activity and those measured directly in the weeks following the accident in London, Leeds and Cumbria.     

The comparative analysis of gene and structural somatic mutations in inhabitants of Orel district areas contaminated with radionuclides as a result of Chernobyl accident

The results of comparative analysis of gene and structural mutations found in peripheral blood lymphocytes of inhabitants of Orel district areas contaminated with radionuclides as a result of Chernobyl accident are presented. The average level of 137Cs contamination in those areas ranged about 22-113 kBq/m2. In the study group was found the enhanced frequency of somatic cells with gene and structural mutations compared with laboratory control level by synchronous applying a T-cell receptor (TCR) loci mutation assay and cytogenetic analysis of unstable aberrations. The case-control comparison was carried out using the measured mutation frequencies and cases of various thyroid gland sickness recognized by ultrasonic examination. The cytogenetic assay did not show the statistical difference between healthy group and subjects with thyroid gland sickness. The average frequency of TCR loci mutation cells in the subjects with thyroid gland sickness was found to be statistically higher comparing with healthy persons. This finding was true for each study region and for Orel district in total. The subgroup of subject exposed in utero in 1986, soon after accident was analyzed. Both cytogenetic and TCR loci mutation assays shown enhancement of average mutation frequency in somatic cells in the subjects of this subgroup with thyroid gland sickness comparing with healthy persons.     

Retrospective biodosimetry among United States radiologic technologists

Measurement of chromosome translocations in peripheral blood lymphocytes has been used to quantify prior exposure to ionizing radiation, including for workers exposed to low, chronic doses. We assessed translocation frequencies in a subset of U.S. radiologic technologists to substantiate ionizing radiation dose estimates developed for 110,418 technologists who worked between 1916 and 1984. From 3,441 cohort members known to have begun working before 1950, we selected a sample of 152, stratified by estimated cumulative dose, over-sampling from higher-dose categories and excluding persons with a prior cancer diagnosis, a personal or family history of chromosomal instability disorders, or a current history of smoking. Estimates of film-badge dose ranged from less than 10 cSv to more than 30 cSv. Blood samples, obtained in 2004, were analyzed by fluorescence in situ hybridization (FISH) whole chromosome painting by simultaneously labeling chromosomes 1, 2 and 4 in red and 3, 5 and 6 in green. Translocations were scored in 1800 well-spread metaphase cells and expressed per 100 cell equivalents (CE) per person. Linear Poisson regression models with allowance for overdispersion were used to assess the relationship between estimated occupational red bone marrow absorbed dose in cGy and translocation frequency, adjusted for age, gender and estimated red bone marrow absorbed dose score from personal diagnostic procedures. We observed 0.09 excess translocations per 100 CE per cGy red bone marrow dose (95% CI: -0.01, 0.2; P = 0.07), which is similar to the expected estimate based on previous cytogenetic studies (0.05 excess translocations per 100 CE per cGy). Despite uncertainty in the estimates of occupational red bone marrow absorbed doses, we found good general agreement between the doses and translocation frequencies, lending support to the credibility of the dose assessment for this large cohort of U.S. radiologic technologists.     

Cytogenetic disturbances and immunoreactivity in patients with measles and influenza

The number of lymphocytes with cytogenetic aberrations is increased in patients with measles and influenza. Considerable changes in immunoreactivity of the organism can be observed during measles and influenza. Correlation analysis suggests that in measles and influenza there exists an inversely proportional connection between the number and functional activity of T lymphocytes and the level of cytogenetic disturbances in them. Indices of B immune system and the level of cytogenetic aberrations in influenza were characterized by directly proportional correlation while in measles the type of correlation depended on the intervals of observation.     

Cytogenetic effects of cyclophosphamide on human lymphocytes in vivo and in vitro

A comparative study of cytogenetic effects in human lymphocytes caused in vivo by cyclophosphamide (CP) after intravenous injection and in vitro by exposure of plasma of the same patients was carried out. It was found that the frequency of induced chromosome aberrations (CA) and sister-chromatid exchanges (SCE) increased linearly for SCE and exponentially for CA within the 'dose' of alkylating activity of CP metabolites. Parameters of 'cytogenetic effect-dose' in vivo and in vitro coincided. The intensity of cytogenetic effects varied between individuals.     

Cytogenetic activity of the pesticides cyclophos and alvison, their components and metabolites

Two new pesticide preparations of cyclophos and alvison, a number of their components, two alvison metabolites have been studied to reveal their cytogenetic activity. According to the investigation in vivo the mutagenic effect of cyclophos manifests itself only with toxic doses. Professional contacts with the pesticide don't induce chromosome mutation in human peripheral lymphocytes. The alvison preparations generate chromosome mutations in somatic cells of people and animals. The components and metabolites of alvison have shown no visible genetic activity during in vivo and in vitro experiments.     

Mutagenicity studies with nitrofurans. I. Mutagenicity of nitrofurylacrylic acid for mammals

Cytogenetic analysis of mouse bone-marrow cells, the dominant lethal test in mice and the cytogenetic analysis of human peripheral lymphocytes in vitro were used to study the mutagenicity of 3-(5-nitro-2-furyl)acrylic acid (5-NFA) for mammals. The bone-marrow cytogenetic analysis was performed in female mice exposed to 5-NFA administered intraperitoneally in single doses of 15--120 mg/kg and in 5 repeated doses of 15 and 30 mg/kg, intragastrically in single doses of 30--240 mg/kg and 5 repeated doses of 30 and 60 mg/kg, and perorally for 12 weeks to 5-NFA concentration of 10, 100 and 1000 mg 5-FNA/1 in drinking water. The bone-marrow analysis was performed in this case after 12 days, 3, 4, 6, 8, 10 and 12 weeks exposure. No increase in chromosome damage attributable to dosing with 5-NFA occurred in any of these experiments. Experiments in which mice were exposed to 5-NFA in drinking water for 12 weeks and then treated with a single i.p. dose of 2 mg of the mutagen TEPA [trix-(1-aziridinyl)phosphine oxide] per kg revealed that, at a concentration of 1000 mg 5-NFA/1, the clastogenic activity of TEPA was reduced to that in untreated animals. The dominant lethal test was performed in male mice exposed to 5-NFA applied intraperitoneally in single doses of 40--120 mg/kg and in 5 repeated doses of 10--30 mg/kg, intragastrically in 5 repeated doses of 20--60 mg/kg, and perorally for 4 weeks in drinking water containing 5-NFA at concentrations of 10, 100, 316 and 1000 mg/l. No significant differences were detected between the exposed and control groups of animals. Experiments in which male mice were exposed to 5-NFA in drinking water and treated after the 4-week exposure to 5-NFA with 1 mg TEPA/kg revealed that a concentration of 1000 mg 5-NFA/1 reduced TEPA-induced dominant lethality to within control values. A reduction in male fertility was observed after the single or repeated 5-NFA doses, but no changes when 5-NFA was applied in drinking water. The cytogenetic analysis of human peripheral lymphocytes exposed in vitro for the last 24 h of culture to concentrations of 1--100 micrograms 5-NFA/Ml did not show any compound-related chromosomal changes. The results of dominant-lethal and bone-marrow cytogenetic studies in mice after consumption of drinking water containing 1000 mg of 5-NFA/1 for 12 weeks and dosed subsequently with TEPA suggests that 5-NFA has some antimutagenic activity. Because none of the studies reported revealed any compound-related genetic activity, the results suggest that 5-NFA is not a chromosome-breaking agent in mammals.     

BUdR as a tracer of the possible mutagenic activity of Pb++ in human lymphocyte cultures.

The method of SCE was used as an indicator of the possible mutagenic activity of lead acetate in in vitro cultures of human lymphocytes. After determining the optimal concentration of BUdR, the cultures were treated with increasing doses of the metal. The negative results obtained with this method led us to examine other parameters, in particular the classical cytogenetic aberrations.     

The cytogenetic effect of natural modifiers of mutagenesis in a human lymphocyte culture: the modification of the mutagenic effect by recombinant interferon in vitro in the lymphocytes of bronchial asthma patients and of healthy donors]

The significant protective effect of recombinant interferon in the cultures of lymphocytes of healthy donors and patients with bronchial asthma has been revealed. The cytogenetic damage were stimulated by alkylating agents thioTEPA and photrin during their administration at the stages Gi-S of the cell cycle. No differences were revealed in the action of mutagens and protector in the patients and healthy persons.