Development of a database: DACTARI for a radiotoxic element ranking methodology.

Dosimetric impact studies aim at evaluating potential radiological effects of chronic or acute releases from nuclear facilities. A methodology for ranking radionuclides (RN) in terms of their health-related impact on the human population was first developed at CEA with specific criteria for each RN that could be applied to a variety of situations. It is based, in particular, on applying physico-chemical criteria to the complete RN inventory (present in the release or in the source term) and on applying norms related to radiation protection and chemical toxicology. The initial step consisted in identifying and collecting data necessary to apply the methodology, with reference to a previous database of long-lived radionuclides (LLRN, with half-lives ranging from 30 to 10(14) y) containing 95 radionuclides. The initial results have allowed us to identify missing data and revealed the need to complete the study for both toxic and radiotoxic aspects. This led us to the next step, developing a specific database, DAtabase for Chemical Toxicity and Radiotoxicity Assessment of RadIonuclides (DACTARI), to collect data on chemical toxicity and radiotoxicity, including acute or chronic toxicity, the chemical form of the compounds, the contamination route (ingestion, inhalation), lethal doses, target organs, intestinal and maternal-foetal transfer, drinking water guidelines and the mutagenic and carcinogenic properties.

Hair dosimetry following neutron irradiation.

Use of hair as a biological dosimeter of neutron exposure was proposed a few years ago. To date, the (32)S(n,p)(32)P reaction in hair with a threshold of 2.5 MeV is the best choice to determine the fast neutron dose using body activation. This information is essential with regards to the heterogeneity of the neutron transfer to the organism. This is a very important parameter for individual dose reconstruction from the surface to the deeper tissues. This evaluation is essential to the adapted management of irradiated victims by specialized medical staff. Comparison exercises between clinical biochemistry laboratories from French sites (the CEA and COGEMA) and from the IRSN were carried out to validate the measurement of (32)P activity in hair and to improve the techniques used to perform this examination. Hair was placed on a phantom and was irradiated at different doses in the SILENE reactor (Valduc, France). Different parameters were tested: variation of hair type, minimum weight of hair sample, hair wash before measurement, delivery period of results, and different irradiation configurations. The results obtained in these comparison exercises by the different laboratories showed an excellent correlation. This allowed the assessment of a dose-activity relationship and confirmed the feasibility and the interest of (32)P measurement in hair following fast neutron irradiation.

Study of uranium transfer across the blood-brain barrier.

Uranium is a heavy metal which, following accidental exposure, may potentially be deposited in human tissues and target organs, the kidneys and bones. A few published studies have described the distribution of this element after chronic exposure and one of them has demonstrated an accumulation in the brain. In the present study, using inductively coupled plasma mass spectrometry (ICP-MS) for the quantification of uranium, uranium transfer across the blood-brain barrier (BBB) has been assessed using the in situ brain perfusion technique in the rat. For this purpose, a physiological buffered bicarbonate saline at pH 7.4 containing natural uranium at a given concentration was perfused. After checking the integrity of the BBB during the perfusion, the background measurement of uranium in control rats without uranium in the perfusate was determined. The quantity of uranium in the exposed rat hemisphere, which appeared to be significantly higher than that in the control rats, was measured. Finally, the possible transfer of the perfused uranium not only in the vascular space but also in the brain parenchyma is discussed.

Radiation-induced chromosome damage in astronauts' lymphocytes.

The increased number of manned space missions has made it important to estimate the biological risks encountered by astronauts. As they are exposed to cosmic rays, especially ions with high linear energy transfer (LET), it is necessary to estimate the doses they receive. The most sensitive biological dosimetry used is based on the quantification of radiation-induced chromosome damage to human lymphocytes. After the space missions ANTARES (1992) and ALTAIR (1993), we performed cytogenetic analysis of blood samples from seven astronauts who had spent from 2 weeks to 6 months in space. After 2 or 3 weeks, the X-ray equivalent dose was found to be below the cytogenetic detection level of 20 mGy. After 6 months, the biological dose greatly varied among the astronauts, from 95 to 455 mGy equivalent dose. These doses are in the same range as those estimated by physical dosimetry (90 mGy absorbed dose and 180 mSv equivalent dose). Some blood cells exhibited the same cytogenetic pattern as the 'rogue cells' occasionally observed in controls, but with a higher frequency. We suggest that rogue cells might result from irradiation with high-LET particles of cosmic origin. However, the responsibility of such cells for the long-term effects of cosmic irradiation remains unknown and must be investigated.

Aneuploidy in human lymphocytes: an extensive study of eight individuals of various ages.

Data on aneuploidy from a prospective study on a large number of lymphocyte metaphases (over 1000 in 72-h and 100 in 48-h cultures) per individual from eight healthy donors of various ages are reported. Chromosome losses were dependent on culture time, being significantly more frequent in 72-h than in 48-h cultures. All donors exhibited various degrees of aneuploidy which increased with age in women. This increase resulted essentially from X chromosome losses, as previously reported. Although the rate of aneuploidy limited to autosomes was similar in newborns and in adults, the distributions of the missing autosomes were different. In the two newborns studied, autosome aneuploidy was random. In the adults, a significant inverse correlation with autosome lengths was observed. The inverse correlation between chromosome lengths and losses may be explained by selective pressure against monosomic cells in the adults.

Cytogenetic study of five cases of lung adenosquamous carcinomas.

The cytogenetic study of five cases of untreated adenosquamous carcinoma of the lung allows us to propose a number of characteristic anomalies. All tumor cells were hyperdiploid, with a mean chromosome number ranging from 59 to 83, and had many clonal chromosome rearrangements. The chromosomes the most frequently affected by these rearrangements were, by decreasing order, 1, 3, and 15; 7 and 8; and 17. No recurrent breakpoints were observed in euchromatic regions, most breaks (45/66) involving juxtacentromeric heterochromatin or immediately adjacent regions. Although chromosome 3 was frequently rearranged, no recurrent deletions of its short arm were observed.

Recurrent chromosome aberrations in human lung squamous cell carcinomas.

Cytogenetic study of seven cases of previously untreated lung squamous cell carcinomas (SQC) is reported. Chromosome numbers vary from 38 to 538, with a majority of hypotriploid karyotypes with complex rearrangements. The numbers of recurrent imbalances were evaluated in considering the average number of chromosomes or chromosome segments in each analyzed metaphase and for each case. In decreasing order of frequency, deficiencies for 3p, 5q, 8p, Y, 5p, 10p, 13, and, to a lesser degree, for 8q, 9, 10q, 11pter, 14, 15, and 21 were observed; the excesses principally involve 1q, 3q, and 7q. In three tumors, homogeneously staining regions were observed at various chromosome sites. Most chromosome rearrangements occurred after breakage in constitutive heterochromatin, and no recurrent breakpoints were found in euchromatin except 11p15. The major consequences of these anomalies may be chromosomal imbalances, leading to hemizygosity and perhaps related to gene dosage, rather than to alterations of genes.

Chromosomal aberrations induced by low-dose gamma-irradiation. Study of R-banded chromosomes of human lymphocytes.

The effect of low-dose (0-0.5 Gy) gamma-radiations was studied on R-banded chromosomes from lymphocytes of healthy donors of various ages. In cells from newborns, an increase of chromosome damage roughly proportional to the dose was found. In lymphocytes from young adults chromosomal aberrations were not detected at doses of 0.05 and 0.1 Gy, and in lymphocytes from old adults chromosomal aberrations were not detected at doses of 0.05 and 0.1 Gy, and in lymphocytes from old adults not even at 0.2 Gy. The difficulty in detecting aberrations in lymphocytes from adults is largely due to a considerable background of chromosomal anomalies which should be borne in mind in dosimetry studies. The rate of induction largely depends on the types of rearrangements. One-break terminal deletions are efficiently induced at 0.1 and 0.2 Gy and are the best indicators of exposure at these doses. At 0.5 Gy, the frequencies of 2-break lesions, i.e., dicentrics and reciprocal translocations, increase, whereas that of deletions decreases.

Acquired chromosome rearrangements in human lymphocytes: effect of aging.

A prospective study of structural rearrangements occurring in normal lymphocytes was carried out. For each of two newborns and four young and two old adults, about 1000 metaphases from 72-h and 120 from 48-h cultures were studied. The frequency of rearrangements between bands 7p14, 7q35, 14q11.2 or 14q12 and 14qter, which is on the average about 0.003, is higher in newborns (0.0043) than in adults (0.0024). Conversely, the rearrangements involving other bands, which have a frequency of 0.025 on the average, are more frequent in old adults (f = 0.038) than in young adults (f = 0.025) and newborns (f = 0.013). The first type of rearrangement, which occurs in utero, may correspond to immunoglobulin and related gene rearrangements. The other rearrangements seem to accumulate progressively and may reflect exposure to mutagens. It is import to discriminate these two types of rearrangements when studying the effect of low doses of mutagens.

Isoacentric and isocentric chromosomes originating after deletions of human chromosomes.

The analysis of a sample of 100 isoacentric (IA) and isocentric (IC) chromosomes, which had originated from spontaneous or radiation-induced deletions in human lymphocytes, is reported. IC and also IA have a strong tendency to be formed after breakage in juxtacentromeric heterochromatin. When euchromatic regions are involved, the breaks are not distributed at random since they frequently occur at places where juxtacentromeric heterochromatin exists in other primate species. It is assumed that intercalary structures conserving some of the properties of heterochromatin exists in human chromosomes in intercalary positions.