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1.
J Exp Med ; 148(5): 1338-50, 1978 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-722241

RESUMEN

The expression of terminal deoxynucleotidyl transferase (TdT) in the thymus and bone marrow of irradiated mice has been examined. Mice given the leukemogenic regimen of irradiation of four weekly doses of 175 rads starting at 1 mo of age show a long-term elimination of TdT activity in the bone marrow and a reduction of TdT activity in thymocytes. In such mice, the reappearance of normal levels of TdT in the thymus appears to only be associated with the onset of overt leukemia. This effect on TdT expression was shown to be uniquely associated with the leukemogenic regimen of irradiation in that nonleukemogenic irradiation or variations such as bone marrow reconstitution or age which reduce leukemias did not show the same phenotypic effects on TdT expression. The basis for the loss of TdT-positive cells was shown not to be due to the lack of the requisite factors involved in differentiation, but rather to the ability of leukemogenic doses of irradiation to reduce or eliminate an inducible bone marrow stem cell. These results are discussed with respect to the possible mechanisms involved in radiation-induced leukemias in mice.


Asunto(s)
ADN Nucleotidilexotransferasa/metabolismo , ADN Nucleotidiltransferasas/metabolismo , Leucemia Experimental/enzimología , Leucemia Inducida por Radiación/enzimología , Animales , Médula Ósea/enzimología , Relación Dosis-Respuesta en la Radiación , Ganglios Linfáticos/enzimología , Ratones , Ratones Endogámicos C57BL , Bazo/enzimología , Timectomía , Timo/enzimología
2.
J Exp Med ; 147(3): 708-18, 1978 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-632747

RESUMEN

Terminal deoxynucleotidyl transferase (TdT) expression in bovine serum albumin (BSA) gradient-fractionated bone marrow cells was examined in NIH Swiss nu/nu and thymectomized C57BL/6 mice. In nude mice, TdT levels were approximately 10% of those of thymus-bearing littermates. In C57BL/6 mice, thymectomy caused a time-dependent loss of TdT activity in bone marrow cells. To determine whether or not not the apparent thymic requirement for TdT expression in bone marrow was mediated by thymic hormones, we examined the effects of thymosin fraction 5. Treatment of either NIH Swiss nu/nu or thymectomized C57BL/6 mice with thymosin fraction 5 restored the levels of TdT activity in BSA gradient-fractionated bone marrow cells to normal. Moreover, treatment of BSA gradient-fractionated bone marrow cells from NIH Swiss nu/nu or thymectomized C57BL/6 mice in tissue culture with thymosin fraction 5 induced TdT expression. In tissue culture, TdT induction was optimal with 25 ng/ml of thymosin fraction 5, it occurred within 6 h, and it was completely inhibited by actinomycin D. The effect was specific in that neither control nor spleen fraction 5-treated cells were induced to express TdT. These data demonstrate that TdT expression in bone marrow cells is under the direct control of thymic polypeptide hormones.


Asunto(s)
Médula Ósea/enzimología , ADN Nucleotidiltransferasas/biosíntesis , Timosina/farmacología , Hormonas del Timo/farmacología , Animales , Células Cultivadas , Inducción Enzimática/efectos de los fármacos , Ganglios Linfáticos/enzimología , Ratones , Ratones Desnudos/metabolismo , Bazo/enzimología , Timectomía
3.
J Exp Med ; 144(6): 1406-23, 1976 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-63529

RESUMEN

The expression of endogenous ecotropic viruses in radiation-induced thymomas of C57BL/6 mice was examined. Competition radioimmunoassays for AKR MuLV gp71, p30, and p12 were used for viral antigen expression. 3 of 40 lymphomas had readily detectable ecotropic gp71 at levels of 95-689 ng/mg protein; the remainder of the tumors had no detectable gp71 (less than 1.0 ng/mg protein). 30 thymomas were characterized by the presence of MuLV p30 at levels of 1-10 ng/mg protein, levels that were comparable to those found in thymus extracts from age-matched, nonirradiated control. 10 tumors were characterized by having p30 levels of 10-30 ng/mg protein. In one tumor significant levels of AKR MuLV p12 were detectable. Since B-tropic and N-tropic viruses from C57BL/6 mice have glycoproteins (gp71) indistinguishable from AKR MuLV gp71 and the N-tropic virus had a p12 serologically identical to AKR MuLV p12, these results demonstrate that overt endogenous B-tropic virus was detectable in 2 of 40 thymomas and endogenous N-tropic virus was detectable in 1 of 40 thymomas. The lack of overt expression of gp71 or p12 was also confirmed by cytotoxicity assays using monospecific antisera to these viral proteins. Radiation-induced lymphomas were also examined for the presence of reverse transcriptase after chromatography of tissue extracts on poly G-Sepharose. One tumor, which was characterized by the lack of gp71, also had no detectable reverse transcriptase; whereas one tumor with gp71 was characterized by readily detectable levels of reverse transcriptase in cellular extracts. The presence of viral RNA was examined using AKR cDNA. Low levels of RNA capable of hybridizing with AKR cDNA were found in age-matched, nonirradiated mice; these hybrids had Tm's of 72 degrees C, while hybrids with AKR MuLV 70S RNA had Tm's of 80 degrees C. In 1 of 12 thymomas the concentration of hybridizable RNA and the Tm of the hybrids were identical to control values. In 9 of 12 thymomas the concentration of hybridizable sequences increased approximately three-to fivefold and the Tm of these hybrids varied from 73 to 75 degrees C. In 1 of 12 thymomas the concentration of hybridizable sequences increased over 100-fold, hybridized completely with AKR MuLV cDNA, and the hybrids had Tm's of 79 degrees C. This thymoma was also characterized by the presence of the AKR MuLV type of gp71 and p12. One tumor was characterized by a 10-to 100-fold increase in hybridizable sequences, which only partially hybridized with AKR MuLV cDNA, and hybrids had a Tm of 73 degrees C. This tumor was characterized by the presence of AKR MuLV gp71 but not AKR MuLV p12. The results taken together demonstrate that overt endogenous ecotropic virus expression is only rarely detectable in radiation-induced thymomas of C57BL/6 mice.


Asunto(s)
Antígenos Virales/análisis , Virus de la Leucemia Murina , Leucemia Inducida por Radiación , Ratones Endogámicos C57BL/microbiología , ARN Viral/análisis , Timoma/microbiología , Neoplasias del Timo/microbiología , Virus de la Leucemia Murina AKR , Animales , Reacciones Antígeno-Anticuerpo , Pruebas Inmunológicas de Citotoxicidad , Virus de la Leucemia Murina/inmunología , Leucemia Inducida por Radiación/microbiología , Ratones , ADN Polimerasa Dirigida por ARN/análisis , Timoma/etiología , Neoplasias del Timo/etiología
4.
Cancer Res ; 35(1): 237-41, 1975 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-162863

RESUMEN

The interaction between line 1 carcinomas growing s.c. and their spontaneous (or artificial) metastases has been studied in syngeneic BALB/c mice. In contrast to typical murine tumor systems, concomitant immunity, or the ability of primary tumors to suppress the growth of metastases, develops very slowly in this system, such that the metastases that are shed within the first week of tumor growth survive and ultimately prove lethal to the host. The rate of development of concomitant immunity can be accelerated by increasing the hosts' tumor burden or decelerated by exposure of the hosts to X-rays prior to tumor transplant. This cancer system offers, therefore, an excellent model for the therapy of metastases that cannot be obtained with typical murine tumors.


Asunto(s)
Adenocarcinoma Bronquioloalveolar/inmunología , Línea Celular , Neoplasias Pulmonares/inmunología , Metástasis de la Neoplasia , Animales , Femenino , Inyecciones Intravenosas , Inyecciones Subcutáneas , Masculino , Ratones , Ratones Endogámicos BALB C , Trasplante de Neoplasias , Neoplasias Experimentales/inmunología , Factores de Tiempo , Trasplante Homólogo
5.
Cancer Res ; 35(7): 1654-61, 1975 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-1131827

RESUMEN

When given intratracheal injections of a suspension of benzo(alpha)pyrene-ferric oxide, rats and hamsters showed striking species differences in the response of their respiratory tracts to the carcinogen. Hamsters produced squamous metaplasia of the trachea and large bronchi; in contrast, squamous cell nodules of bronchioloalveolar origin developed in rats within a few weeks after carcinogen application. The different sites of the early proliferative and metaplastic responses correlated in their location with the sites of later tumor development. There were no obvious differences between the two species in retention of benzo(alpha)pyrene in the lungs or tracheas. A species difference was observed, however, in the localization of the benzo(alpha)pyrene in the tracheal tissues using ultraviolet fluorescence microscopy. Carcinogen was found to be present in the epithelium of hamsters but not in the epithelium of rats, suggesting a species difference in penetration of carcinogen from the lumen into the tracheal tissues.


Asunto(s)
Benzopirenos , Compuestos Férricos , Hierro , Neoplasias del Sistema Respiratorio/inducido químicamente , Especificidad de la Especie , Animales , Benzopirenos/administración & dosificación , Benzopirenos/metabolismo , Neoplasias de los Bronquios/inducido químicamente , Embrión de Pollo , Cricetinae , Perros , Pulmón/metabolismo , Neoplasias Pulmonares/inducido químicamente , Microscopía Fluorescente , Neoplasias Experimentales/inducido químicamente , Ratas , Ratas Endogámicas , Neoplasias del Sistema Respiratorio/patología , Factores de Tiempo , Tráquea/metabolismo , Neoplasias de la Tráquea/inducido químicamente , Rayos Ultravioleta
6.
Transplantation ; 28(3): 212-7, 1979 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-91250

RESUMEN

Ultraviolet (UV)-irradiated mice were compared with unirradiated mice for their susceptibility to primary and transplanted tumors etiologically unrelated to UV radiation. Although UV-irradiated mice are unable to reject transplants of highly antigenic syngeneic tumors induced by UV light, the growth of syngeneic, non-UV-induced tumors generally was not accelerated in these animals. Furthermore, UV-irradiated mice were no more susceptible to the induction of primary leukemias, mammary tumors, or sarcomas than were unirradiated animals. Tests of immune responses to weak transplantation antigens showed that UV-irradiated mice rejected H-Y-incompatible skin grafts as vigorously as did normal animals, and that the primary in vitro cytotoxic responses of spleen cells from UV-irradiated mice to trinitrophenyl (TNP)-modified syngeneic cells and to Hh antigens were unaffected. We conclude that the susceptibility of UV-irradiated mice to challenge with UV-induced tumors represents a selective unresponsiveness, and that it is not attributable to a generalized deficiency in the immune response to tumor-specific antigens or to weak transplantation antigens.


Asunto(s)
Transformación Celular Neoplásica/efectos de la radiación , Memoria Inmunológica , Neoplasias Inducidas por Radiación/inmunología , Rayos Ultravioleta , Animales , Antígenos de Neoplasias , Proteínas Portadoras/inmunología , Epítopos , Antígenos de Histocompatibilidad , Ratones , Ratones Endogámicos AKR , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Neoplasias Experimentales/inmunología
14.
J Immunol ; 117(2): 620-5, 1976 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-950464

RESUMEN

The distribution of terminal deoxynucleotidyl transferase (TdT) peak I and peak II in thymuses and peripheral lymphoid tissues was examined in a variety of mouse strains in relation to tumor burden and age. TdT peak I was found to be present in all strains at comparable levels, which did not change with age. TdT peak II levels were also comparable for the strains examined at 1 week of age. In contrast to peak I, however, in NIH Swiss and AKR mice, peak II activity decreased rapidly at 2 weeks of age and by 6 weeks of age less than 2% of the initial activity remained. In C57BL/6 mice there was a similar loss of peak II activity with age although this change started at about 4 months of age and by 8 months of age approximately 15% of the initial activity remained. These changes did not appear to be due to the presence of an inhibitor. Leukemic C57BL/6 and AKR mice were also examined for TdT. Both strains characteristically had TdT peak I in peripheral lymphoid tissues infiltrated with transformed thymocytes. AKR mice had only TdT peak I in the thymus, whereas C57BL/6 thymuses had both peak I and II at levels comparable to age-matched controls. No aberrant distribution of TdT was observed in a spontaneous reticulum cell sarcoma or Rauscher MuLV-induced erythroblastosis.


Asunto(s)
Leucemia Inducida por Radiación/enzimología , Linfocitos/enzimología , Linfoma/enzimología , Nucleotidiltransferasas/metabolismo , Envejecimiento , Animales , Ratones , Ratones Endogámicos AKR , Ratones Endogámicos C57BL , Especificidad de la Especie , Neoplasias del Timo/enzimología
15.
J Immunol ; 119(2): 494-9, 1977 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-301893

RESUMEN

The distribution of terminal deoxynucleotidyl transferase (TdT) peaks I and II, in single cell suspensions of thymuses, bone marrow, and peripheral lymphoid organs fractionated in discontinuous bovine serum albumin gradients, was examined in a variety of mouse strains and Fischer 344 rats to relate the normal patterns of thymocyte differentiation to the leukemic process. TdT peaks I and II were found in fractions A (10 to 23%), B (23 to 26%), and C (26 to 29%) of the thymus of both normal and leukemic C57BL/6 mice, whereas only peak I was found in the same fractions of AKR mice. TdT in bone marrow was found mainly in fraction A in both normal and leukemic mice. The specific activity of TdT in this fraction, which comprises only 1 to 5% of the total bone marrow cell population, was similar to that of the thymus. The cell population of fraction A of the bone marrow was found to increase (10 to 15-fold) in leukemic mice. Only low levels of TdT activity were found in either whole or fractionated bone marrow of athymic NIH Swiss (nu/nu) mice.


Asunto(s)
Células de la Médula Ósea , Médula Ósea/enzimología , ADN Nucleotidiltransferasas/metabolismo , Leucemia Experimental/enzimología , Linfocitos T/enzimología , Timo/enzimología , Animales , Diferenciación Celular , Isoenzimas/metabolismo , Leucemia Experimental/etiología , Leucemia Inducida por Radiación/enzimología , Leucemia Inducida por Radiación/etiología , Ratones , Ratones Endogámicos , Ratones Desnudos , Ratas , Ratas Endogámicas F344
16.
Cancer Treat Rep ; 62(11): 1749-55, 1978 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-310341

RESUMEN

Terminal deoxynucleotidyl transferase (TdT) is uniquely associated with the major thymocyte population and a minor bone marrow population which is separable on bovine serum albumin gradients. The expression of TdT in the bone marrow subpopulation is under thymic regulation in that this population is significantly reduced in nude mice or is lost with time after thymectomy. The expression of TdT in athymic mice can be induced both in vivo and in vitro by thymosin fraction 5 or by beta3, a peptide purified from thymosin fraction 5. The optimal concentration of beta3 in the in vitro induction of TdT is approximately 10 ng/ml. These results demonstrate that thymic hormones control the early differentiation of prothymocytes in the bone marrow.


Asunto(s)
ADN Nucleotidilexotransferasa/biosíntesis , ADN Nucleotidiltransferasas/biosíntesis , Células Madre Hematopoyéticas/efectos de los fármacos , Linfocitos T/efectos de los fármacos , Timosina/farmacología , Hormonas del Timo/farmacología , Animales , Médula Ósea/enzimología , Diferenciación Celular/efectos de los fármacos , Inducción Enzimática/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Ratones Desnudos
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