RESUMO
The 24-h and 72-h incorporation of 59Fe into circulating erythrocytes in mice were strongly inhibited by a single subcutaneous dose of T-2 toxin given 1 h before the radioisotope. The system is extremely sensitive, since a significant effect was detected with T-2 toxin doses as low as 0.30 mg/kg, which is about one-tenth of the LD50 in the BALB/c strain used for the present study. In the treated animals no initial changes were observed in the blood 59Fe levels or in the rate of radioisotope clearance from plasma, indicating that the toxin does not interfere with iron absorption or transport. It is concluded that the inhibition observed reflects the damage produced by this toxin on reticulocytes and/or erythroblasts, and therefore this method could be of value as a very sensitive means of studying the risk of erythropoietic injury produced by dietary exposure to trichothecene mycotoxins.
Assuntos
Eritrócitos/metabolismo , Ferro/metabolismo , Toxina T-2/toxicidade , Animais , Relação Dose-Resposta a Droga , Injeções Intraperitoneais , Injeções Subcutâneas , Radioisótopos de Ferro/metabolismo , Dose Letal Mediana , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Toxina T-2/sangueRESUMO
Previous studies revealed that a single dose of T-2 toxin produces a strong inhibition of the 59Fe incorporation into circulating erythrocytes in mice. In the present work it is shown that equivalent doses of T-2 toxin (0.30 mg/kg and above) can produce a relative depletion of granulocyte-macrophage colony-forming cells (CFU-GM) in the bone marrow of treated mice. In additional experiments, both the 59Fe uptake into erythrocytes and the bone marrow CFU-GM were measured as a function of dose and time after a single administration of T-2 toxin. It was found that the initial inhibitory effects are reverted between 24 h and 72 h and that in some cases there is even a significant increase over the normal values, indicating that there may be a compensatory activation of the hematopoietic system. The results presented here suggest that extremely small doses of T-2 toxin can produce a significant degree of bone marrow cytotoxicity and therefore even low level dietary contamination may be of concern.
Assuntos
Sistema Hematopoético/efeitos dos fármacos , Toxina T-2/toxicidade , Animais , Dieta , Relação Dose-Resposta a Droga , Eritrócitos/metabolismo , Contaminação de Alimentos/análise , Granulócitos/citologia , Granulócitos/efeitos dos fármacos , Hematopoese/efeitos dos fármacos , Células-Tronco Hematopoéticas/efeitos dos fármacos , Ferro/farmacocinética , Ferro/farmacologia , Radioisótopos de Ferro , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Sensibilidade e Especificidade , Toxina T-2/análise , Fatores de Tempo , Tricotecenos/toxicidadeRESUMO
The 59Fe uptake into bone marrow and spleen was measured as a function of time after a single dose of T-2 toxin in mice (2.0 mg/kg, sc). It was found that, after a potent initial inhibition, there was a striking difference in the apparent repair capacity of both tissues: in spleen activity rapidly recovered (48-72 hr), whereas in bone marrow it remained significantly depressed for much longer (about 21 days). These results might be taken to indicate that T-2 toxin produces some sort of irreversible damage to bone marrow. However, working with T-2 toxin-related splenectomized mice it was found that bone marrow erythropoietic activity was rapidly repaired, indicating that, under the conditions of the present experiments, there is no irreversible injury to the marrow haematopoietic or stromal cells. Further studies will be required using multiple doses or continuous toxin exposure in order to test the potential for long-lasting residual injury to the haematopoietic tissue. The present results show that the uptake of 59Fe into both spleen and bone marrow provides a rapid and sensitive method, suitable for primary evaluation of the extent of the erythropoietic damage produced by trichothecene mycotoxins.
Assuntos
Medula Óssea/efeitos dos fármacos , Eritropoese/efeitos dos fármacos , Baço/efeitos dos fármacos , Toxina T-2/toxicidade , Animais , Injeções Subcutâneas , Radioisótopos de Ferro , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Toxina T-2/administração & dosagemRESUMO
Total nucleated cellularity and total erythroid cell populations were measured in spleen and bone marrow of mice at different times after treatment with 3 daily doses of T-2 toxin (2.0 mg/kg). It was found that the initial depletion of hematopoietic cells produced by the toxin was rapidly reverted in spleen, giving way after 48 hr to a significant hypercellularity which after 10 days was 2.5 times the normal levels, but this effect was not observed in bone marrow, which slowly recovered normal cellularity after 5 days. The cytological analysis revealed that there was a highly significant shift in the ratio of erythroid to non-erythroid cells, since erythroid cell populations increased by about 8-fold in spleen and nearly 2-fold in bone marrow between 10 and 35 days after intoxication. In order to test the integrity of the hematopoietic reserve capacity, a hemorrhagic stress was produced in intoxicated animals at 10-50 days after toxin exposure. It was found that the erythroid response capacity was significantly higher in the intoxicated animals compared to anemic controls. The results suggest that the initial cytotoxic damage produced by T-2 toxin in the hematopoietic system is followed by a significant erythroid hypercellularity, which can confer an increased capacity for response to a hemorrhagic emergency.
Assuntos
Células Precursoras Eritroides/efeitos dos fármacos , Hemorragia/fisiopatologia , Toxina T-2/toxicidade , Animais , Células da Medula Óssea/efeitos dos fármacos , Hematopoese/efeitos dos fármacos , Sistema Hematopoético/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Baço/citologia , Baço/efeitos dos fármacosRESUMO
Agar cultures of toxigenic Aspergillus parasiticus NRRL 2999 were exposed to phosphine (PH3), in levels ranging from 0 to 2000 ppm (vol/vol). It was found that with PH3 concentrations of 400 ppm or higher the growth of the fungus was totally arrested. When PH3 was vented and the agar plates were exposed to open air, 100% of the initial CFU developed into fully grown colonies after PH3 levels below 300 ppm, but at higher PH3 concentrations only 50% of the colonies developed. The same strain of A. parasiticus was inoculated into high moisture corn under conditions highly favorable for aflatoxin production, and it was exposed to a range of PH3 levels. After exposure to 500 ppm PH3, both fungal growth and aflatoxin synthesis resumed shortly after elimination of the toxic gas, but after exposure to PH3 levels of 1000 ppm and higher, the physical appearance of the contaminated corn was remarkably changed, showing reduced mycelial growth and almost complete absence of green pigmentation. In addition, aflatoxin synthesis was totally absent for the remainder of the experiment (20 days). These results strongly suggest that exposure to PH3 levels of 1000 ppm or higher could bring about persistent metabolic changes in surviving Aspergillus organisms.