[Show abstract][Hide abstract] ABSTRACT: Bacterial metabolism of 4-chlorobiphenyl (4-CB), a model compound of polychlorinated biphenyls, has been investigated. Grown in the presence of 4-CB, Gram-negative strain B-206 oxidized the non-chlorinated ring to yield 2,3-dihydroxy-2,3-dihydro-4′-chlorobiphenyl, 3,4-dihydroxy-3,4-dihydro-4′-chlorobiphenyl, as well as their corresponding 2,3 and 3,4 catechol analogues, 2-hydroxy-4′-chlorobiphenyl and 4-hydroxy-4′-chlorobiphenyl. The intermediate catechols were further oxidized to yield 2-hydroxy-6-oxo-6-(4′-chlorophenyl)-hexa-2,4-dienoic acid, 2-hydroxy-6-oxo-(4′-chlorophenyl)-hexanoic acid, 5-oxo-5-(4′-chlorophenyl)-pentanoic acid, 4-oxo-4-(4′-chlorophenyl)-butanoic acid, 4-chlorocinnamic acid and 4-chlorobenzoic acid, which accumulates in the culture broths. The hydroxylated biotransformation products were characterized by gas chromatographic/mass spectrometric analysis as trimethylsilyl (TMS) and d9-TMS derivatives, whereas metabolites with vicinal diols were also analysed as their n-butylboronate derivatives. Gas chromatographic/mass spectrometric features of the metabolite derivatives are presented and 4-CB biodegradation pathways are discussed.
[Show abstract][Hide abstract] ABSTRACT: Recent progress especially in the field of gene identification and expression have raised more attention on genetic susceptibility to cancer possibly enhanced by radiation. Radiation therapists are mostly concerned by this question since hypersensitive patients may suffer from adverse effects in normal tissues following a standard radiation therapy and normally sensitive patients could benefit from higher doses of radiation for better treatment of their malignant tumors. Although only a small percentage of individuals are "hypersensitive" to radiation effects, all medical specialists using ionising radiation should be aware of this new progress in medical knowledge. The present paper reviews the main pathologies (diseases, syndromes...) known or strongly suspected to be associated with a hypersensitivity to ionizing radiation. Then the main tests capable of detecting in advance such pathologies are analyzed and compared. Finally guidelines are provided, especially to the radiation therapists to limit the risk of severe complications (or even deaths) for this specific subset of patients suffering from a genetic disorder with a susceptibility to radiations.
The quarterly journal of nuclear medicine: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR) 01/2001; 44(4):347-54.
[Show abstract][Hide abstract] ABSTRACT: The effectiveness of fission neutrons is compared to that of gamma rays and X rays with regard to the induction of malignancies in male Sprague-Dawley rats. The analysis is based on autopsy results. It is focused on tumors that tend to be present in animals dying early, which is indicative of a high degree of lethality. The relative biological effectiveness (RBE) is deduced from a comparison of the cumulative hazard functions. Different nonparametric models-the constant relative risk model, a time shift model, and an acceleration model-are employed in the comparison, and the resulting values of RBE are seen to be substantially independent of the choice of model. The results are in good agreement with earlier studies of nonlethal lung tumors in the same series of experiments. At neutron doses of 20 to 60 mGy, the RBE of fission neutrons is about 50.
Radiation Research 11/2000; 154(4):412-20. · 2.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Everyone is exposed to radiation from natural, man-made and medical sources, and world-wide average annual exposure can be set at about 3.5 mSv. Exposure to natural sources is characterised by very large fluctuations, not excluding a range covering two orders of magnitude. Millions of inhabitants are continuously exposed to external doses as high as 10 mSv per year, delivered at low dose rates, very few workers are exposed above the legal limit of 50 mSv/year, and referring to accidental exposures, only 5% of the 116,000 people evacuated following the Chernobyl disaster encountered doses above 100 mSv. Epidemiological survey of accidentally, occupationally or medically exposed groups have revealed radio-induced cancers, mostly following high dose-rate exposure levels, only above 100 mSv. Risk coefficients were derived from these studies and projected into linear models of risk (linear non-threshold hypothesis: LNT), for the purpose of risk management following exposures at low doses and low dose-rates. The legitimacy of this approach has been questioned, by the Academy of sciences and the Academy of medicine in France, arguing: that LNT was not supported by Hiroshima and Nagasaki studies when neutron dose was revisited; that linear modelling failed to explain why so many site-related cancers were obviously non-linearly related to the dose, and especially when theory predicted they ought to be; that no evidence could be found of radio-induced cancers related to natural exposures or to low exposures at the work place; and that no evidence of genetic disease could be shown from any of the exposed groups. Arguments were provided from cellular and molecular biology helping to solve this issue, all resulting in dismissing the LNT hypothesis. These arguments included: different mechanisms of DNA repair at high and low dose rate; influence of inducible stress responses modifying mutagenesis and lethality; bystander effects allowing it to be considered that individual cellular responses reflected in fact the results of multiple cellular interactions. Following the conclusion of the French Academy of medicine, LNT modelling resulted in public anxiety by changing an hypothetical residual risk at low doses into a real one, calling on regulators, continuously, for a more and more severe control of tiny sources which may result in considerable collective doses when considered as being exposed to billions of people for hundreds of years. Examples were provided that showed that the perception of risk of radioactive sources was not related to the severity of the risk itself but to the importance attributed to the situation by the media. In some instances, such as those resulting from the loss of gammagraphy sources, it resulted in a dangerous underestimate of the necessary remedial actions.
Comptes Rendus de l Académie des Sciences - Series III - Sciences de la Vie 08/2000; 323(7):633-40.
[Show abstract][Hide abstract] ABSTRACT: Radiotoxicology is a science aiming firstly to estimate the biological effects induced by radiation in workers and general population after internal contamination of radionuclides, secondly evaluate the risk on health. After internal contamination, the analysis of biokinetics of radioactive compounds allow to understand their behaviour in the body. Those complex processes describe routes of radionuclide intake, direct blood uptake or transfer of soluble form to blood from deposit area, urine and fecal excretions, distribution and retention of radionuclides in different target organs. These processes are modelled to establish mathematical calculations. Data obtained are important to the interpretation of bioassay measurement for initial activity deposit expressed in becquerel (Bq: transformation.s-1) and committed effective dose calculation, expressed in sievert (Sv). This committed effective dose corresponds to the absorbed dose expressed in gray (Gy), weighted by a radiation weighting factor related to the quality of radiation and a tissue weighting factor which represents the contribution of the target organ to the total detriment due to effects induced by uniform irradiation of the whole body. This committed effective dose is a specific parameter for risk assessment which characterizes the radiotoxicology as a special part of toxicology.
Comptes rendus des séances de la Société de biologie et de ses filiales 02/1997; 191(5-6):765-75.
[Show abstract][Hide abstract] ABSTRACT: The reproductive toxicity of lead was investigated in NMRI mice exposed to 0.5% lead acetate in drinking water from day 1 of intra-uterine life until 60 days after birth. Compared with control mice, the weights of lead-exposed fetuses and subsequently of the lead-exposed weaned pups, male and female, diminished by 11 and 13% respectively. The lead-exposed male and female offspring of lead-exposed dams were mated with unexposed females and males, to examine the effect of lead exposure on reproductive function. Male fertility was not affected but reduced female fertility was observed: litters were smaller and a smaller number of implantation sites was found in lead-exposed females. In lead-exposed males, the weights of the body, testes and epididymes diminished by about 13%, and seminal vesicle and ventral prostate weights, by about 29%. Testicular histology and the number and morphology of epididymal spermatozoa were normal. The levels of plasma FSH, LH and testosterone, and of testicular testosterone, were not modified. These results suggest that the hypothalamic-pituitary-testicular axis is not adversely affected by the above lead exposure, and that therefore the decreased seminal vesicle and ventral prostate weights might not be the consequence of reduced testosterone levels. The hypothesis that lead has a direct effect on these organs as well as a secondary effect resulting from possibly reduced food consumption by lead-exposed mice cannot be excluded. Consequently, in male NMRI mice, exposure to lead might affect reproductive function by acting directly and/or indirectly on accessory sex organs.
Human & Experimental Toxicology 12/1995; 14(11):872-8. · 1.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The present investigation was aimed at establishing the distribution of 237Np within the different structures of hepatocytes. Rats were contaminated experimentally by intravenous injection of 237Np (V) and the subcellular structures of the liver were separated by ultracentrifugation. Twenty-four hours after contamination, the nuclear and cytosolic fractions bound 54 and 32%, respectively, of the total radionuclide. Purification of the nuclei followed by dissociation of the protein components in medium of increasing ionic strength showed a specific binding of neptunium to the structural proteins of the nuclear matrix.
Radiation Research 09/1995; 143(2):214-8. · 2.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To clarify the mechanism of the action of lead on male reproductive function, adult male rats were injected intraperitoneally (i.p.) with lead acetate (8 mg/kg/day of lead), 5 days a week for 35 days. Despite this high dose, germ cells and Sertoli cells did not appear to be major targets of lead. However, lead determination in the reproductive organs showed that the accessory sex glands are such a target. Epididymal function was unchanged. In lead-exposed rats, plasma and testicular testosterone dropped by about 80%, but plasma luteinizing hormone (LH) only dropped by 32%. After luteinizing hormone releasing hormone (LHRH) stimulation of the pituitary, the plasma LH level reached the control one, but plasma testosterone remained significantly reduced by 37%. The sharp decrease in the testosterone:LH ratio in lead-exposed rats, combined with the significant reduction of intertubular tissue volume in the testes, indicate impaired Leydig cell function.
[Show abstract][Hide abstract] ABSTRACT: Using magnetic resonance (MR) and isotopic imaging to investigate the cerebral alterations after highdose single-fraction irradiation on a pig model. We assessed the nuclear magnetic resonance (NMR) relaxation times as early markers of radiation injury to the healthy brain.
A total of 17 animals was studied; 15 irradiated and 2 unirradiated controls. Pigs were irradiated with a 12 MeV electron beam at a rate of 2 Gy/min. Ten animals received 40 Gy at the 90% isodose, five animals received 60 Gy, and two animals were unirradiated. The follow-up intervals ranged from 2 days to 6 months. T1-weighted scans, T2-weighted scans, and scintigrams were performed on all animals to study neurological abnormalities, cerebral blood flow, and blood-brain barrier (BBB) integrity. T1 and T2 relaxation times were measured in selected regions of interest (ROIs) within the irradiated and contralateral hemispheres. A ratio T1 after irradiation/T1 before irradiation, and a ratio T2 after irradiation/T2 before irradiation, were calculated, pooled for each dose group, and followed as a function of time after irradiation.
Scintigraphy visualized the brain perfusion defect and BBB disruption in all irradiated brains. The ratio T2 after irradiation/T2 before irradiation was proportional to the effective dose received. The T2 ratio kinetics could be analyzed in three phases:an immediate and transient phase, two long-lasting phases, which preceded compression of the irradiated lateral ventricle, and edema and necrosis at later stages of radiation injury, respectively. The magnetic resonance imaging (MRI) observations correlated well with histological analysis.
The results show that quantitative imaging is a sensitive in vivo method for early detection of cerebral radiation injury. The reliability and dose dependence of T2 relaxation time may offer new opportunities to detect and understand brain pathophysiology after high-dose single-fraction irradiation.
International Journal of Radiation OncologyBiologyPhysics 05/1995; 32(1):121-8. · 4.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study was designed to compare the translocation from lung of the Pu contained in the pure and mixed industrial oxides PuO2 and (U,Pu)O2. The latter had a Pu content of 20% w/w. For this purpose, young adult male rats and male and female baboons were exposed to a single inhalation of these oxides. Two baboons were exposed to the reference PuO2, i.e. 239PuO2. Rats were killed under anaesthesia 1, 15, 30, 90 and 180 days after exposure, and baboons, also under anaesthesia, 1 year thereafter. The results indicate that lung retention of Pu was independent of the oxide inhaled, but was smaller in rat (12-15% of the initial pulmonary burden, 6 months after exposure) than in baboon (56-80% of this burden, 1 year after exposure). In rat, Pu translocation kinetics were similar for the two industrial oxides, but as from day 15 after inhalation until 6 months thereafter, measurement of Pu deposits in the liver and skeleton showed that translocation of Pu from the mixed oxide was 2-3 times greater than that from the industrial Pu oxide. In baboon, the largest amounts of Pu were retained in the lung and thoracic lymph nodes for the three oxides inhaled. Pu translocation to the liver, skeleton and kidneys, and also urinary Pu excretion, were greater after inhalation of the mixed oxide than after inhalation of the industrial and reference Pu oxides. Nevertheless, the amount of mixed oxide Pu translocated to these sites and excreted in urine remained under 3% of the initial pulmonary burden.
International Journal of Radiation Biology 04/1995; 67(3):373-80. · 1.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This work describes quantitative MRI assessment of primate brain maturation. Nine young baboons were followed from the age of one to 30 months. Assessment of myelination was based on the gray/white matter contrast on MR images and the evolution of T2 relaxation time respectively. The brain maturation began in the posterior fossa and progressed to the olfactory bulbs corresponding to decreasing white matter T2 values. Relaxation parameters provide new opportunities to trace the myelination process in vivo.
Journal of Medical Primatology 03/1995; 24(2):87-93. · 1.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Lead is an environmental pollutant which has received much attention, partly because of the particular sensitivity of children to this element. As regards the consequences of exposure to lead during fetal life or childhood, epidemiological studies have so far focused on its neuropsychological effects and little is known about the consequences of fetal or childhood exposure for reproduction. With respect to animals, the reproductive toxicity of lead in males exposed during prenatal life or the suckling period has only been considered in a few studies. Four such studies concerned the rat, the most current model of lead toxicity for male reproduction; two of studies considered the long term effects (i.e. during adulthood) of moderate in utero lead exposure, another covered the prenatal and neonatal periods and focused on the possible impact of lead intoxication on steriodogenesis before weaning, while the remaining study dealt with pituitary hormone level at the end of lead gavage in newborns. None of these investigations compared the effects of exposure during prenatal life to those of exposure via lactation, or the early effects (at about weaning time) to the long-term consequences during adulthood. Because of the paucity of data on these points, we conducted two experiments: in one, rats were exposed to lead prenatally, and in the other via maternal milk. In both cases male reproductive function at weaning and adulthood was examined. 12 refs., 1 fig., 2 tabs.
Bulletin of Environmental Contamination and Toxicology 03/1995; 54(2):266-72. · 1.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 1. The effects of lead poisoning during pregnancy were tested on female Sprague-Dawley rats that inhaled 5 mg m-3 lead oxide for 13 days during gestation. At the end of gestation, the respective blood lead levels of dams and fetuses were 71.1 and 83.2 micrograms 100 ml-1, indicating lead poisoning. 2. In the 90 day-old male offspring of the exposed dams, testis weight and histology, and epididymal weight and sperm reserve, were all similar to those of control males. Spermatozoa mobility and morphology were normal. 3. Also similar to control values were the pituitary weight in these male offspring, their plasma FSH, LH and testosterone levels, and the weight of their ventral prostate and seminal vesicles, the targets of the sexual hormones. 4. When male and female offspring of exposed dams were mated, their fertility was normal, with no increase in prenatal death or malformations, and no changes in the size or sex ratio of litters. 5. These results indicate that, under our experimental conditions, lead oxide inhalation by rats during pregnancy did not perturb reproductive function in their male offspring.
Human & Experimental Toxicology 05/1994; 13(4):241-6. · 1.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Sprague-Dawley rats were exposed to Co 60 irradiation (3 Gy) at different ages. Rats were distributed among sham-control (618 males and 120 females) and exposed groups: foetus (66 males and 65 females), 3 month-old (304 males), and 9 month-old (120 males and 60 females). The incidence of brain tumours was 5.3% in male control rats and nil in female control rats. Brain tumour incidence decreased in 9 month-old rats (3.3%), and increased from 6.6% in 3 month-old rats to 15.2% in male foetuses and 12.3% in female foetuses. Age at incidence of brain tumours decreased in irradiatiated animals. Astrocytomas were the more susceptible type of brain tumours to radiocarcinogenesis.
Comptes Rendus de l Académie des Sciences - Series III - Sciences de la Vie 04/1994; 317(3):277-81.
[Show abstract][Hide abstract] ABSTRACT: It has been previously established that lung cancer could be induced in rats by exposure to radon and radon daughters. Although the oat-cell carcinomas that are common in humans were not found in rats, other histological types of lung carcinomas, especially squamous cell carcinomas and primitive lung adenocarcinomas, were similar to those observed in humans. A dose-effect relationship was established for cumulative doses varying from 25 to 3000 working-level-months (WLM), which was similar for medium and high cumulative doses to that observed in uranium miners. This experimental protocol was also used to study the potential cocarcinogenic effects of other environmental or industrial airborne pollutants such as tobacco smoke, mineral fibers, diesel exhausts, or minerals from metallic mine ores that may act synergistically with radon exposure. In rats exposed to radon and tobacco smoke combined, the incidence of lung cancers was higher by a factor of 2-4 according to the cumulative radon exposure and the duration of tobacco smoke exposure. When mineral fibers were injected intrapleurally, an increased incidence of malignant thoracic tumors was observed in rats exposed to radon and fibers combined, but synergistic effects resulted in additivity. With diesel exhausts or minerals from metallic ores, a slight, nonsignificant increase in the incidence of lung carcinomas was observed compared with rats exposed to radon alone. These results demonstrated that it is possible to establish the potential cocarcinogenic action, showing either multiplicative, additive, or no effect of various environmental or industrial airborne pollutants combined with radon exposure. This radon model is valid for investigating possible interactions between two occupational exposures.
Environmental Health Perspectives 02/1994; 102(1):64-73. · 7.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recent epidemiologic studies suggested that some histologic types of carcinomas were preferentially induced in the lung by irradiation, whatever the mode of exposure and the radiation quality. Since smoking and other environmental airborne pollutants may be strong confounding factors in humans, we have investigated whether histological subtypes were dependent or not on the mode of exposure, in a large series of 9000 rats exposed to external and internal sources at high and low Linear Energy Transfer. Despite comparable overall risk coefficients in rats and humans, our results show that histological types are influenced not only by dose but also by radiation quality and heterogeneity of dose delivering. We suggest that extrapolation from one group to an other take this information in consideration.
Comptes Rendus de l Académie des Sciences - Series III - Sciences de la Vie 02/1994; 317(1):90-3.