RESUMO
Two leukemogenic viral populations were derived from a radiation leukemia virus of the C57BL mouse. One (FB), in which only B-tropic virus could be detected, was obtained in vivo by serial passage of cell-free extract in newborn rats. The second (3C), a complex containing at least B-tropic and xenotropic viruses, was produced in vitro by a permanent cell line (13-3C) established from the spleen of a virus-infected C57BL mouse. In molecular hybridization experiments, the 70S RNA of Gross leukemia virus hybridized 96 and 78% of FB and 3C radioactive complementary DNA's, respectively, with a relatively high thermal stability of the duplexes formed. In contrast, the 70S RNA of Rauscher leukemia virus hybridized 23 and 20% of the FB and 3C DNA probes, respectively, with a low thermal stability. The rat-grown FB virions exhibited 50% genome homology with the viruses produced in vitro on the 13-3C cells. Finally, hybridizing the FB and 3C probes with normal or leukemic mouse spleen DNA's resulted in 89 to 100% homology. The rat-grown virions did not appear to contain detectable rat cellular DNA sequences, while about 20 complete copies of their nucleotide sequences were detected in covalent linkage with FB-infected rat spleen DNA. These findings strongly support the endogenous murine origin of the investigated virions.
Assuntos
Vírus da Leucemia Murina/metabolismo , Leucemia Experimental/microbiologia , Leucemia Induzida por Radiação/microbiologia , RNA Viral/metabolismo , Infecções Tumorais por Vírus/microbiologia , Vírus AKR da Leucemia Murina/metabolismo , Animais , Linhagem Celular , DNA Viral/metabolismo , Camundongos , Hibridização de Ácido Nucleico , Ratos , Vírus Rauscher/metabolismoRESUMO
In mice, endogenous retroviruses are known to be activated during the course of radiation osteosarcomagenesis. Using the Southern blotting procedure, we have studied the presence of somatically acquired proviruses in genomic DNA isolated from seven primary 90Sr induced osteosarcomas and one osteosarcoma cell line, 0-127a1, of the CF1 mouse strain. Specific hybridization probes demonstrated the presence of newly integrated ecotropic proviruses in four primary tumors. Probably, clonally integrated proviruses were present at distinct locations in different subpopulations of tumor cells, reflecting tumor heterogeneity. Genomic DNA isolated from cultured osteosarcoma cells contained different additional MCF-related proviruses. No proviruses were found integrated in the vicinity of c-myc, but a large domain containing the complete c-myc gene was found amplified in one primary tumor (greater than 22 kbp) and in 0-127a1 cells (greater than 39 kbp). Our data suggest that activated retroviruses are not essential for the development of radiogenic osteosarcomas in CF1 mice, but they might be responsible for the deregulated expression of a growth promoting gene in some bone tumor cells.
Assuntos
Transformação Celular Viral/efeitos dos fármacos , Neoplasias Induzidas por Radiação/genética , Osteossarcoma/genética , Proteínas Proto-Oncogênicas/genética , Radioisótopos de Estrôncio/farmacologia , Animais , Enzimas de Restrição do DNA , DNA de Neoplasias/genética , Amplificação de Genes , Regulação da Expressão Gênica , Camundongos , Neoplasias Induzidas por Radiação/microbiologia , Osteossarcoma/microbiologiaRESUMO
The mode of action of radioprotective glycans is not understood. In view of the known importance of cell migration in haematology, on the one hand, and of carbohydrates in homing processes, on the other, we have investigated the effect of several glycans on blood-borne arrest of lymphoma cells. Radioprotective glycans (but not heparin) modified the arrest of injected cells in the spleen. Altered recirculation and homing processes may play a role in the radioprotective properties of glycans.
Assuntos
Linfoma/patologia , Células Neoplásicas Circulantes , Polissacarídeos/farmacologia , Protetores contra Radiação/farmacologia , Animais , Adesão Celular , Movimento Celular , Feminino , Injeções Intravenosas , Camundongos , Camundongos Endogâmicos , Especificidade de Órgãos , Linfócitos T , Células Tumorais CultivadasRESUMO
Three C57BL/Ka mice were inoculated with RadLV/VL3, a thymotropic and leukemogenic virus population released by the permanent BL/VL3 cell line, which was derived from a C57BL/Ka lymphoma induced by radiation leukemia virus (RadLV). The neoplastic thymus and bone marrow cells from these mice were grown until the cultures became permanently established, and their DNAs were examined for the presence of virus-related sequences by restriction enzyme analysis. All six cell lines displayed identical EcoRI and BamHI restriction fragments, not found in control C57BL/Ka DNA and accounting for the presence of more than one novel provirus. The primary and secondary tumors were thus clonal and, even though they were obtained from different animals, possessed identical integration sites. The BL/VL3 cell line also displayed the clonal appearance of novel proviral sequences, partly identical, with respect to location and BamHI restriction pattern, to those found in the RadL/VL3-induced tumor cell lines. Neither radiation-induced tumors, nor cloned cell lines derived therefrom, whether producing leukemogenic virus (BL/RL12-P) or not (BL/RL12-NP), displayed the presence of novel virus-related sequences when compared with control tissues. Our results strongly suggest not only that, as described in the case of avian leukosis virus-induced tumors of the chicken, RadLV-induced leukemogenesis might be a consequence of cellular gene activation by promotor insertion, but also that more than one integration site might be involved. Radiation-induced tumorigenesis might be initiated by a comparable mechanism, not requiring the participation of a virus.
Assuntos
Sítios de Ligação Microbiológicos , DNA de Neoplasias , Genes Virais , Vírus da Leucemia Murina/genética , Linfoma/microbiologia , Lisogenia , Neoplasias Induzidas por Radiação/microbiologia , Animais , Linhagem Celular , Transformação Celular Viral , Elementos de DNA Transponíveis , Eletroforese em Gel de Ágar , Camundongos , Camundongos Endogâmicos C57BL , Infecções Tumorais por Vírus/microbiologiaRESUMO
Intravenous administration of 60 mg/kg of a polysaccharide (MNR, MNZ, GLP/BO4, GLP/BO5) significantly decreases the mortality of mice exposed to a single dose of X rays. The dose reduction factors (DRF) obtained for MNZ, MNR, GLP/BO4, and GLP/BO5 given intraperitoneally 15 min before exposure were 2.16, 1.93, 1.80, and 1.94, respectively. The DRF was not increased when MNZ or GLP/BO4 were combined with injection of AET before X-ray exposure. The LD50 for the CFUs exposed in vivo in mice was 1.13 Gy for the treated mice and 0.75 Gy for the nontreated mice. This corresponds to a DRF of 1.6. The DRF calculated from the slope is 1.27.
Assuntos
Células-Tronco Hematopoéticas/efeitos da radiação , Polissacarídeos/farmacologia , Protetores contra Radiação/farmacologia , Animais , Relação Dose-Resposta à Radiação , Células-Tronco Hematopoéticas/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Rhodotorula , Saccharomyces cerevisiae , Irradiação Corporal TotalRESUMO
The advantages gained by a combined treatment of different chemical protectors on short-term lethality of X-irradiated adult male mice have been studied. The following compounds were given alone or in a mixture of two or three compounds: 16,16-dimethyl PGE2 (PGE2), cysteine (Cys), glucan, glutathione (GSH), 5-hydroxytryptamine (5-HT), mercaptoproprionylglycine (MPG), or WR-2721. The survival of mice treated before X irradiation with the optimal dose of each radioprotector given separately shows that WR-2721 and 5-HT yield the best protection with dose reduction factors (DRFs) of 2.2 and 1.7, respectively. Cysteine, glucan, PGE2, MPG, and GSH, with DRFs of 1.4, 1.4, 1.2, 1.1, and 1.1, respectively, are less efficient radioprotectors. When PGE2 was combined with a low dose of WR-2721 (200 mg/kg), the protection increased in a synergistic way. The increase in protection offered by a combination of PGE2 with Cys, glucan, GSH, or 5-HT is less marked and the effect obtained is only additive. A synergistic action is also obtained with a combination of WR-2721 (200 mg/kg) and 5-HT (8 mg/kg) (DRF 2.7).
Assuntos
Fatores Imunológicos/uso terapêutico , Lesões Experimentais por Radiação/prevenção & controle , 16,16-Dimetilprostaglandina E2/uso terapêutico , Amifostina/uso terapêutico , Animais , Cisteína/uso terapêutico , Quimioterapia Combinada , Glucanos/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos , Lesões Experimentais por Radiação/mortalidade , Serotonina/uso terapêuticoRESUMO
A life-span study on male C57BL mice after injection of various doses of 241Am was conducted. The effects on life span were evaluated and the incidence of tumors was determined by procedures that take competing risks into account. Bone tumors were induced in the mice by injections of 22 and 58 Bq 241Am per g. The mice died early from nonneoplastic diseases at the higher dose levels (190, 373, and 1197 Bq 241Am/g). Additionally, spontaneously occurring tumors such as liver carcinomas, lymphosarcomas, and lymphoreticulosarcomas occurred at an enhanced rate with increasing dose level. The data for survival time after 241Am injection and death with bone tumor were compared to data collected previously for 226Ra-injected mice of the same C57BL strain. This enabled direct comparison in the same strain of the effects of the bone-surface seeker 241Am to the effects of the bone-volume seeker 226Ra. The proportional hazards model was applied and the rate of death with bone tumor was 12.9 +/- 5.2 times higher after 241Am injection than after 226Ra injection if the regression covariate was the average dose to the skeleton. The relative risk was 3.5 +/- 1.7 if regressed on the injected radioactivity. The mortality rate after 241Am injection was 20.4 +/- 3.6 times higher than after 226Ra injection if regressed on average dose to the skeleton.
Assuntos
Amerício/toxicidade , Rádio (Elemento)/toxicidade , Amerício/administração & dosagem , Amerício/farmacocinética , Animais , Neoplasias Ósseas/epidemiologia , Neoplasias Ósseas/etiologia , Neoplasias Ósseas/mortalidade , Injeções Intraperitoneais , Expectativa de Vida , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Induzidas por Radiação/epidemiologia , Neoplasias Induzidas por Radiação/mortalidade , Rádio (Elemento)/administração & dosagem , RiscoRESUMO
Survival and causes of mortality were studied in 7- or 21-day-old male C57BL/Cnb mice exposed to 0.5, 1 or 3 Gy of 250 kVp X rays or 0.125, 0.25, 0.5 or 1 Gy of accelerator neutrons (modal energy 3.1 MeV). A total of 1287 animals were used in the experiments. Survival of irradiated animals was reduced significantly only in the mice receiving the highest doses (1 Gy neutrons, 3 Gy X rays ). Mice exposed to the lowest doses (0.125 Gy neutrons, 0.5 Gy X rays) lived significantly longer than controls, apparently reflecting a reduction in non-neoplastic lung and liver diseases. All malignant tumors increased significantly from (and including) doses of 0.5 Gy neutrons and 1 Gy X rays. Hepatocellular carcinoma was the principal contributor to the increase in tumor incidence, at least after exposure to neutrons. No significant increase in hepatocellular carcinoma was seen in 21-day-old mice exposed to X rays. An increase, especially after 3 Gy X rays, was also observed for all leukemias. Controls in the present study lived significantly longer than those in our earlier studies of irradiated adult mice, making a direct comparison of the radiation-induced effects in adult and infant mice difficult. Based on percentage life shortening, it appears that exposure during infancy does not shorten total survival or survival from cancer much more than exposure of adults, although such exposure, especially to neutrons, causes more hepatocellular carcinoma. Due to the nonlinearity of the dose-effect relationships, it is difficult to calculate the RBE of neutrons. For survival time at higher doses an RBE of about 3 is obtained. When the incidence of all malignant tumors and of hepatocellular cancer is fitted to a linear or a linear-quadratic function, an RBE from 5 to 8 is obtained. No RBE can be estimated for hepatocellular carcinoma in mice of an age of 21 days because exposure to X rays does not seem to cause this tumor at that age.
Assuntos
Nêutrons Rápidos/efeitos adversos , Longevidade/efeitos da radiação , Neoplasias Induzidas por Radiação/etiologia , Fatores Etários , Animais , Relação Dose-Resposta à Radiação , Leucemia Induzida por Radiação/etiologia , Neoplasias Hepáticas Experimentais/etiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Radiobiologia , Eficiência Biológica RelativaRESUMO
BALB/c male mice (12 weeks old) were exposed to a single or fractionated exposure of 137Cs gamma rays. The fractionated dose was split into 10 equal doses delivered at an interval of 1 day. The causes and possible causes of spontaneous death were ascertained by autopsy and histological examination, and the data were treated by competing risk analysis. Life shortening followed a linear dose dependency and was about the same for fractionated (38.1 +/- 3.1 days/Gy) as for single (46.2 +/- 4.3 days/Gy) exposure. Death from tumor disease was enhanced and that from nonstochastic lung and kidney diseases was reduced after fractionated compared to single exposure.
Assuntos
Nefropatias/etiologia , Expectativa de Vida , Pneumopatias/etiologia , Neoplasias Induzidas por Radiação/etiologia , Irradiação Corporal Total/efeitos adversos , Animais , Autopsia , Raios gama , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/etiologia , Probabilidade , Doses de Radiação , Irradiação Corporal Total/métodosRESUMO
Male BALB/c mice, 12 weeks old, were given a single exposure of either 137Cs gamma rays or d(50)-Be neutrons at a dose rate of 3 Gy/min. The animals were kept until death, and causes of death or possible causes of death were ascertained by autopsy and histology. The data were evaluated by competing risk methods. The survival time dose-effect curve for both types of exposure was linear and did not differ significantly (slopes: 55.8 +/- 4.0 days/Gy for neutrons and 46.2 +/- 4.3 days/Gy for gamma rays). The incidence of different diseases also was similar for both groups except that more carcinomas, sarcomas, and myeloid leukemias seemed to occur after neutron exposure and that nonstochastic lung and kidney diseases seemed to arise at lower doses.
Assuntos
Nêutrons Rápidos/efeitos adversos , Nefropatias/etiologia , Pneumopatias/etiologia , Neoplasias Induzidas por Radiação/etiologia , Nêutrons/efeitos adversos , Animais , Autopsia , Relação Dose-Resposta à Radiação , Raios gama , Expectativa de Vida , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Probabilidade , Fatores de Tempo , Irradiação Corporal Total/efeitos adversosRESUMO
The possible combined effects of the initiator diethylnitrosamine (DEN) with X rays on cancer induction in C57BL/Cnb mouse liver were evaluated. Four groups of infant mice were treated as follows: with DEN alone, with X rays alone, with DEN + X rays, and with X rays + DEN. Mice in each group were killed at 10-week intervals over 70 weeks. The following parameters were measured: body weight, liver weight, number and size of macroscopic liver lesions, and number and total surface of the different types of microscopic liver lesions. The number of induced liver foci and carcinomas was found to depend essentially on the dose of DEN. X irradiation did not produce any combined effect on the induction of foci and carcinomas when given 7 days before or after DEN administration.
Assuntos
Dietilnitrosamina/administração & dosagem , Neoplasias Hepáticas/etiologia , Neoplasias Experimentais/induzido quimicamente , Neoplasias Induzidas por Radiação , Animais , Camundongos , Camundongos Endogâmicos C57BL , Fatores de TempoRESUMO
C57Bl Cnb mice were exposed to single or fractionated d(50)+Be neutrons or 137Cs gamma-ray exposure at 12 weeks of age and were followed for life-shortening and disease incidence. The data were analyzed by the Kaplan-Meier procedure using as criteria cause of death and possible cause of death. Individual groups were compared by a modified Wilcoxon test according to Hoel and Walburg, and entire sets of different doses from one radiation schedule were evaluated by the procedure of Peto and by the Cox proportional hazard model. No significant difference was found in life-shortening of C57Bl mice between a single gamma and neutron exposure. Gamma fractionation was clearly less effective in reducing survival time than a single exposure. On the contrary, fractionation of neutrons was slightly although not significantly more effective in reducing life span than a single exposure. Life-shortening appeared to be a linear function of dose in all groups studied. The data on causes of death show that malignant tumors, particularly leukemias including thymic lymphoma, and noncancerous late degenerative changes in lung were the principal cause of life-shortening after a high single gamma exposure. Exposure delivered in 8 fractions 3 h apart was more effective in causing leukemias and all carcinomas and sarcomas than one delivered in 10 fractions 24 h apart or in a single session. Following a single neutron exposure, leukemias and all carcinomas and sarcomas appeared to increase somewhat more rapidly with dose than after gamma irradiation. No significant difference in the incidence of leukemias and all carcinomas and sarcomas was noted between a single and a fractionated neutron exposure.
Assuntos
Nêutrons Rápidos , Leucemia Induzida por Radiação/mortalidade , Longevidade/efeitos da radiação , Neoplasias Induzidas por Radiação/mortalidade , Nêutrons , Animais , Radioisótopos de Césio , Raios gama , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Doses de Radiação , Eficiência Biológica RelativaRESUMO
The possible combined effects of the initiator diethylnitrosamine (DEN)+neutrons on the induction of foci, adenomas and carcinomas in the livers of C57BL/Cnb mice were evaluated. Four groups of infant mice were treated as follows: DEN alone, neutrons alone, DEN followed by neutrons and neutrons followed by DEN. Ten mice in each group were killed at 10-week intervals over 70 weeks. The following parameters were measured: body weight, liver weight, number and size of superficial macroscopic liver lesions, and number and total surface area of the different types of microscopic liver lesions. The rate of appearance of foci increased significantly at different times when a dose of 0.125 Gy of neutrons was administered 7 days before or after a dose of 1.25 micrograms of DEN. No significant differences were observed in the total surface area of foci and/or adenomas and carcinomas when increasing doses of neutrons were given 7 days before or after the administration of 1.25 and 2.5 micrograms of DEN.
Assuntos
Dietilnitrosamina/toxicidade , Neoplasias Hepáticas Experimentais/etiologia , Nêutrons , Animais , Peso Corporal/efeitos dos fármacos , Peso Corporal/efeitos da radiação , Cocarcinogênese , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/efeitos da radiação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Tamanho do Órgão/efeitos dos fármacos , Tamanho do Órgão/efeitos da radiaçãoRESUMO
Male C57Bl/Cnb and BALB/c mice were exposed to single and fractionated d(50) + Be neutrons or 137Cs gamma rays at 12 weeks of age and were followed for life-shortening and disease incidence as ascertained by autopsy and histological examinations at the time of spontaneous death. Fractionation schedules used were 10 exposures at 24-h intervals and 8 exposures at 3-h intervals for gamma rays, and 8 exposures at 3-h intervals for neutrons. The data were analyzed by the Kaplan-Meier procedure using as criteria causes of death and possible causes of death. Individual groups were compared by a modified Wilcoxon test according to Hoel and Walburg (J. Natl. Cancer Inst. 49, 361-372 (1972)). No significant difference was found in C57Bl/Cnb and BALB/c male mice between a single gamma-ray exposure and a single neutron exposure. Gamma-ray fractionation was clearly less effective in reducing survival time than a single exposure. In contrast, fractionation of neutrons was slightly, although not significantly, more effective in reducing survival time than a single exposure. The relative biological effectiveness (RBE) for life-shortening for d(50)-Be neutrons compared to gamma rays is of the order of 1 to 2 for a single exposure to neutrons and between 2 and 3 for fractionated neutrons compared to a single exposure to gamma rays. Neutron irradiation caused somewhat more cancer than gamma irradiation, and the RBE for cancer induction may be higher, probably between 2 and 3 in the range of 1 to 3 Gy, although the present data do not allow a more precise assessment.
Assuntos
Nêutrons , Lesões Experimentais por Radiação/fisiopatologia , Animais , Radioisótopos de Césio , Raios gama , Expectativa de Vida , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , MorbidadeRESUMO
PURPOSE: To review and evaluate the development of effective radiation protectors. OUTLINE: Sulphydryl radioprotectors are the best radioprotectors known today. Their use encounters two great difficulties: their toxicity and the short period during which they are active. The biological response modifiers (BRM), developed mainly in the 1990s, demonstrated some protective effects. They can also modulate radiation injury when given after irradiation. In parallel with the use of single radioprotectors, observations have been made in mice using combined treatments with BRM and other radioprotectors. Low-to-moderate doses of several radioprotective agents acting via different mechanisms markedly improved the degree of protection in rodents while maintaining toxicity within acceptable limits, but applications in man remain doubtful. CONCLUSIONS: No radioprotective drug available today has all the requisite qualities to be an ideal radioprotector. Although combinations of radioprotective drugs acting via different mechanisms markedly improve the degree of protection and keep toxicity to acceptable levels in small rodents, attempts to use such treatments in large mammals have been less successful. It is thus questionable whether chemical protection has any prospects for the future.
Assuntos
Lesões por Radiação/tratamento farmacológico , Proteção Radiológica/métodos , Protetores contra Radiação/uso terapêutico , Animais , Citocinas/uso terapêutico , Quimioterapia Combinada , Previsões , Humanos , Camundongos , Polissacarídeos/uso terapêutico , Prostaglandinas/uso terapêutico , Radiação Ionizante , Radioterapia/efeitos adversos , Roedores , Compostos de Sulfidrila/uso terapêuticoRESUMO
Repeated intraperitoneal injections of ZnNa3-diethylenetriaminepenta-acetate (ZnDTPA), once a week, during 8 successive weeks, and starting 4 days after injection of 58 and 373 kBq 241Am/kg to C57B1 mice, were an effective protection against long-term radiation damage. At both dose levels of 241Am, Zn-DTPA reduced the 241Am concentration in bones by between 33% and 45%, and in the liver by 97%. Mean survival with 241Am was shortened in Zn-DTPA-treated mice, by 17% at the lower dose level and by 70% at the higher dose level. After treatment with DTPA at the lower 241Am level, survival became equal to that of control mice without 241Am, while at the higher level life span was still shortened. After the lower 241Am dose the incidence of bone tumours, liver carcinomas and the total number of all malignant tumours were significantly reduced by chelation therapy. The decrease in bone tumour incidence was proportional to the decrease in 241Am concentration and reduction in cumulative radiation dose in bone after chelation therapy. The incidence of liver carcinomas was reduced to that in non-241Am-injected mice and the reduction was thus proportional to the 97% reduction in 241Am concentration of the liver at the end of chelation therapy. After the higher 241Am dose no tumours showed up in sham-treated mice, probably due to the overkill effect on the cells at risk. In the corresponding Zn-DTPA-treated mice, bone tumours and a few other malignant tumours were observed.
Assuntos
Amerício/toxicidade , Neoplasias Ósseas/etiologia , Ácido Pentético/uso terapêutico , Protetores contra Radiação , Animais , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/prevenção & controle , Relação Dose-Resposta à Radiação , Avaliação Pré-Clínica de Medicamentos , Neoplasias Hepáticas Experimentais/etiologia , Neoplasias Hepáticas Experimentais/mortalidade , Neoplasias Hepáticas Experimentais/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Induzidas por Radiação/etiologia , Neoplasias Induzidas por Radiação/mortalidade , Neoplasias Induzidas por Radiação/prevenção & controle , Fatores de TempoRESUMO
Acute, high dose-rate, exposure of the rat embryo on day 15 post-conception (PC) causes a reduction of brain weight in adult life that is proportional to the dose received. Doses as low as 10 mGy of 600 keV neutrons, from a Van de Graaff accelerator, or 100 mGy of 250 kV X-rays are capable of eliciting a significant effect. The relative biological effectiveness for acute neutron exposure compared with 250 kV X-rays was 3.5. A brain weight reduction was also observed after gamma-ray exposures protracted over 4 or 6 days, during cerebral corticogenesis. The dose-rate reduction factor was only 1.5 for exposure from days 12 to 16 PC and 3.3 for exposure from days 14 to 20 PC. In relation with the decrease in brain weight, the cingulum bundle, a myelinated structure associated with the corpus callosum, displayed a significant reduction in size. The implications of these observations for human exposures are discussed.
Assuntos
Encéfalo/efeitos da radiação , Feto/efeitos da radiação , Animais , Atrofia , Encéfalo/patologia , Feminino , Tamanho do Órgão/efeitos da radiação , Gravidez , Doses de Radiação , Ratos , Ratos Wistar , Eficiência Biológica RelativaRESUMO
Some of the problems related to chemical protection against ionizing radiation are discussed with emphasis on: definition, classification, degree of protection, mechanisms of action and toxicity. Results on the biological response modifyers (BRMs) and on the combination of nontoxic (i.e. low) doses of sulphydryl radioprotectors and BRMs are presented.
Assuntos
Fatores Imunológicos/uso terapêutico , Polissacarídeos/uso terapêutico , Lesões Experimentais por Radiação/prevenção & controle , Protetores contra Radiação/uso terapêutico , Compostos de Sulfidrila/uso terapêutico , Amifostina/uso terapêutico , Amifostina/toxicidade , Animais , Cisteína/uso terapêutico , Cisteína/toxicidade , Relação Dose-Resposta a Droga , Glutationa/uso terapêutico , Glutationa/toxicidade , Camundongos , Polissacarídeos/toxicidade , Lesões Experimentais por Radiação/tratamento farmacológico , Radiação Ionizante , Protetores contra Radiação/classificação , Protetores contra Radiação/toxicidade , Serotonina/uso terapêutico , Serotonina/toxicidade , Compostos de Sulfidrila/toxicidadeRESUMO
The movement through the environment and the toxicity to plants of 99Tc have been studied. However, information is scanty on 99Tc toxicity to mammals even though this is the decisive criterion for assessing the consequences of releases of Tc. A critical tissue could be the thyroid because of its preferential accumulation of Tc and the developing organism because of its greater radiosensitivity; moreover, this toxicity might be enhanced under conditions of a low iodine (I) diet. These questions were studied in rats given large amounts of 99Tc in either a normal or an I-deficient diet for several months starting 2 wk before mating. Newborns were continued on these diets after weaning. The parameters determined were: occurrence of pregnancy and litter size, triiodothyronine and thyroxin in serum, uptake of 131I by the thyroid 24 h after injection, histology of the thyroid and concentration of Tc in tissues of the mothers and their decendants. Thyroid damage, as well as the effects on pregnancy, could be observed after amounts of 10 micrograms Tc g-1 food. Iodine deficiency only slightly influences the 99Tc toxicity. The chemical and radiological toxicity of 99Tc to rats is small. Consequently, it seems unlikely that contamination levels in the environment would ever reach levels that could lead to serious non-stochastic effects, even in the developing organism.