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At least 19 recordsLinked to original sources
PubMed2000

TCR v(beta) repertoire restriction and lack of CDR3 conservation implicate TCR-superantigen interactions in promoting the clonal evolution of murine thymic lymphomas.

Thymic lymphoma development is a multistage process in which genetic and epigenetic events cooperate in the emergence of a malignant clone. The notion that signaling via TCR-ligand interactions plays a role in promoting the expansion of developing neoplastic clones is a matter of debate. To investigate this issue, we determined the TCR V(beta) repertoire of thymic lymphomas induced in AKR/J mice by either endogenous retroviruses or the carcinogen, N-methyl-N-nitrosourea (MNU). Both spontaneous and MNU-induced lymphomas displayed restricted V(beta) repertoires. However, whereas V(beta)6, V(beta)8 and V(beta)9 were expressed by a greater than expected frequency of MNU-induced lymphomas, V(beta)8, V(beta)7, V(beta)13 and V(beta)14 were over-represented on spontaneous lymphomas. The dissimilar TCR V(beta) profiles indicate that different endogenous ligands promote neoplastic clonal expansion in untreated and MNU-treated mice. Although the nature of these ligands is not clear, the lack of conservation in TCR beta chain CDR3 regions among lymphomas that express the same V(beta) segment suggests that endogenous superantigens (SAG), as opposed to conventional peptide ligands, are likely to be involved in the selection process. The biased representation of lymphomas expressing V(beta)6-, V(beta)7- and V(beta)9-containing TCRs that recognize endogenous SAG is consistent with this hypothesis. The finding that Bcl-2 is expressed at high levels in spontaneous and MNU-induced lymphomas suggests that preneoplastic thymocytes may be resistant to SAG-induced clonal deletion. A working model is presented in which preneoplastic clones expressing TCRs that recognize endogenous SAG are selectively expanded as a consequence of sustained TCR-mediated signaling.

Animals↗
PubMed1996

Dendritic cells prevent radiation-induced thymic lymphoma.

Thymic lymphomas develop in C57BL/Ka mice within 36 weeks after split-dose X-irradiation. Lymphoma development can be abrogated in such mice by the injection of syngeneic bone marrow from healthy donors. The abrogation mechanism is unknown, but since bone marrow supplies the thymus with precursors of thymocytes and of dendritic cells, we tested the ability of early thymocytes and of immortalized thymic dendritic cells to abrogate lymphomagenesis. Fifteen weeks after irradiation, mice which had received bone marrow or dendritic cells had an equally low incidence of lymphoma, whereas mice which had received thymocytes or which had been only irradiated developed equally high levels of lymphomas, indicating that thymic dendritic cells played a key role in the prevention of lymphoma development. When thymuses from 15-week survivors were tested for pre-lymphoma cells, those from dendritic cell-treated mice proved to be endowed with a level of lymphomagenic potential intermediate between that from bone marrow-treated mice (nonlymphomagenic) and that from untreated or thymocyte-treated mice (highly lymphomagenic). These data indicate that lymphoma abrogation by bone marrow cells involves the participation of marrow-derived thymic dendritic cells.

Animals↗
PubMed1999

Apoptosis of thymic lymphoma clones by thymic epithelial cells: a putative model for 'death by neglect'.

We have previously described an in vitro system in which thymic epithelial cells induce apoptosis in CD4+ 8+ thymocytes or thymic lymphoma cells, in the absence of an exogenous antigen. A thymic epithelial cell line (TEC) recapitulated the response, by inducing apoptosis in CD4+ 8+ thymocytes of the thymic lymphoma clone, PD1.6. The present study pursues the involvement of the T-cell receptor (TcR) in the response of PD1.6 to TEC. TcR cross-linking did not cause apoptosis of PD1.6, although it induced tyrosine phosphorylation of p95vav. In contrast, TEC did not induce phosphorylation of p95vav but induced apoptosis of PD1.6 cells. These results suggest that TcR-evoked signals are not involved in TEC-induced apoptosis of PD1.6. Intracellular calcium chelation, using BAPTA-loaded PD1.6 cells, diminished TEC-induced apoptosis. Protein kinase C depletion in PD1.6 cells augmented their apoptotic response to TEC. Thus, the response of PD1.6 to TEC is calcium-dependent and inhibited by PKC. Likewise, the apoptotic response of PD1.6 to A23187 was abrogated by PKC activation. PD1.6 cells may represent an immature double positive thymocyte population, which does not undergo negative selection. The interaction of PD1.6 with TEC may thus serve as a model for the TcR-independent 'Death by Neglect', which takes place in the thymus during thymocyte development.

Animals↗
PubMed1981

Cytogenetics of murine thymic lymphomas induced by N-methyl-N-nitrosourea: difference in incidence of trisomy 15 in thymic lymphomas induced in neonatal and adult mice.

Chromosome complements of murine thymic lymphomas induced by an alkylating agent N-methyl-N-nitrosourea (MNUA) were analyzed microscopically and karyotypically using the Q-banding technique. The chemical carcinogen was injected intraperitoneally into either neonatal or 7-week-old CFW/D mice. In addition, thymic lymphomas induced in 7-week-old AKR mice and thymic lymphomas developed spontaneously in this strain were also examined. All six lymphomas induced in neonatal CFW/D had hyperdiploid cell lines that accounted for 90% of the cells analyzed. Chromosome analysis of lymphomas induced in adult DFW/D mice showed that only out of nine lymphomas had predominantly hyperdiploid cell lines. The remaining five lymphomas had diploid modal chromosome number although they also carried a variant line characterized by 41 chromosomes. All eight lymphomas induced in adult AKR mice and six out of seven spontaneous AKR lymphomas showed predominantly diploid modal line. The remaining spontaneous lymphoma had a hyperdiploid stem line of 41 chromosomes. Microscopic and karyotypic analysis further identified trisomy 15 as the regular chromosome abnormality in the hyperdiploid cells in lymphomas of each group, whereas cells with diploid chromosome number had no detectable chromosome abnormality. Additional trisomies were also found, but their appearance was restricted to individual tumors. Thus, the incidence of trisomy 15 in lymphomas induced by MNUA in adult CFW/D and AKR mice, as well as in the spontaneous AKR lymphomas, is significantly lower than that in lymphomas induced in neonatal mice by the same carcinogen.

Age Factors↗
PubMed1997

Deviated overexpression of TCR-beta, TCR-gamma, CD4, and CD8 on thymic lymphomas induced by 1-propyl-1-nitrosourea: destruction of the allelic exclusion of TCR-beta and expression of functional TCR-betagamma heterodimer on a lymphoma, cFTL53.

Thymic lymphomas (FTLs) induced by the chemical carcinogen 1-propyl-1-nitrosourea (PNU) in F344 rats showed deviated overexpression of TCR-beta, TCR-gamma, CD4, and CD8. Even though most FTLs were in the CD4+ CD8+ stage, all FTLs expressed TCR-beta mRNA with TCR-gamma mRNA, but without TCR-alpha mRNA or TCR-delta mRNA. One of the FTLs, cFTL53, expressed two kinds of TCR-beta mRNA and two kinds of TCR-gamma mRNA, but did not express any mRNA of TCR-alpha or TCR-delta. Both alleles of TCR-beta loci were rearranged on cFTL53. cDNA cloning and sequencing analysis showed that one TCR-gamma mRNA, Vgamma4-Jgamma1-Cgamma1, and both TCR-beta mRNA, Vbeta2-Dbeta2-Jbeta2.1 and Vbeta19-Dbeta2-Jbeta2.1-Cbeta2, on cFTL53 were in the productive form, while the other TCR-gamma mRNA, Vgamma1-Jgamma4-Cgamma4L, was not. Both TCR beta-chains and a TCR gamma-chain were expressed on cFTL53, making a novel set of TCR-betagamma heterodimer. Cross-linking of TCR-betagamma heterodimer on cFTL53 resulted in a calcium flux, indicating that TCR-betagamma works as a signal transduction receptor. Thus, there are four strange phenomena on FTLs; CD4 and CD8 are expressed without TCR-alphabeta or TCR-gammadelta, TCR-beta mRNA and TCR-gamma mRNA were expressed simultaneously without TCR-alpha and TCR-delta mRNA on FTLs, the allelic exclusion of TCR-beta was destroyed in cFTL53, and a novel set of functional TCR-betagamma heterodimer was expressed on cFTL53.

Alleles↗
PubMed1984

Development of thymic lymphomas by oral administration of N-nitroso-N-propylurea and establishment of transplantable lines of thymic lymphoma in F344 rats.

Forty-eight female F344/DuCrj rats were given a 400-ppm solution of N-nitroso-N-propylurea (CAS: 816-57-9) continuously in their drinking water. Thymic lymphomas were induced most frequently (85%) followed by duodenal tumors (48%). Sixteen tumors were examined by the immunofluorescence inhibition test for murine leukemia virus-related antigens; 15 were negative and the other was weakly positive. Twenty-six tumors were intraperitoneally and subcutaneously transplanted syngeneically; 25 (96%) were successfully transplanted intraperitoneally and 24 (92%) subcutaneously. The serial intraperitoneal transplantation was continued, and 22 lines of transplantable lymphoma in an ascites form were established. In almost all tumor lines, tumor cells took in a high percentage of recipient rats and caused the death of the recipients within 12-23 days. The thymus, liver, spleen, greater omentum, and lymph nodes were frequently invaded by transplanted tumor cells. The tumor lines were considered to be of T-cell lineage.

Administration, Oral↗
PubMed1987

Development of prelymphoma cells committed to thymic lymphomas during radiation-induced thymic lymphomagenesis in B10 mice.

Intrathymic (i.t.) as well as i.p. injection of thymus cells from B10.Thy-1.1 mice manifesting overt thymic lymphomas, 4 months after split-dose irradiation, into B10.Thy-1.2 recipient mice resulted in the development of donor-type T-cell lymphomas, indicating that they contained "autonomous" lymphoma cells. In contrast, injection of thymus cells from apparently nonleukemic mice 1 month after split-dose irradiation resulted in the development of donor-type tumors only when they were injected i.t., suggesting that thymus cells from these mice contained "preneoplastic" cells that will eventually develop into thymic lymphomas under the influence of thymic microenvironment. These "thymus-dependent" preneoplastic cells were termed "thymic prelymphoma cells." With the use of i.t. injection assay, it was shown that these thymic prelymphoma cells were detected in 26.1% (6 of 23) of the test donor thymuses when examined at 14 days and in more than 63% (15 of 24 and 14 of 22) when examined at 21 and 31 days after irradiation. To examine the possibility that thymic prelymphoma cells might appear first in the bone marrow before they become detectable within the thymuses of the split-dose-irradiated mice, bone marrow cells from B10.Thy-1.1 donors recovered at 8, 14, 21, and 33 days after split-dose irradiation were also injected i.t. into B10.Thy-1.2-recipient mice. The results indicated that none of these recipients developed donor-type T-cell lymphomas, suggesting that bone marrow is not the first site of the appearance of thymic prelymphoma cells.

Animals↗
PubMed2002

Myeloid, B and T lymphoid and mixed lineage thymic lymphomas in the irradiated mouse.

Thymic lymphoma is a very common spontaneous and/or induced malignancy in both inbred mice and in transgenic mouse models of human cancer. Although a thymic lymphoma is defined as thymus-dependent T-cell malignancy, diagnostic criteria vary between studies and considerable heterogeneity has been reported. To define and classify the thymic lymphomas that arose in our study of X-irradiated (CBA/HxC57BL/6)F1, F1 backcross and F1 intercross mice, 66 thymic lymphomas were immunogenotyped for immunoglobulin heavy chain (IgH) and T-cell receptor beta (TCRbeta) gene rearrangements, and/or analysed for expression of lineage-specific markers and allelic loss on chromosome 4. The data indicate that 33% of the thymic lymphomas are very similar to mouse radiation-induced acute myeloid (AML) and mixed lineage (IgH(R), TCRbeta(G)) pre-B lympho-myeloid (L-MLs) leukaemias, 33% are mixed lineage (IgH(R), TCRbeta(R)) B/T lymphoid and <33% can be described as single lineage (IgH(G), TCRbeta(R)) T-cell malignancies. As the myeloid and L-ML leukaemias are not thymus-dependent this suggests that a malignant myeloid or pre-B lympho-myeloid cell can colonize the spleen to give an AML or L-ML leukaemia, or can colonize the thymus where TCRbeta gene rearrangement(s) may be induced to give the mixed lineage thymic lymphomas. Thus, assuming the single lineage T-cell thymic lymphomas fulfil the criteria of a thymus-dependent T-cell malignancy, thymic lymphomas are comprised of at least three distinct malignancies.

Animals↗
PubMed2004

Suppression of thymic lymphomas and increased nonthymic lymphomagenesis in Trp53-deficient mice lacking inducible nitric oxide synthase gene.

Trp53-deficient mice spontaneously develop lymphomas, mainly of thymic origin, although the molecular mechanism remains largely unknown. As several interaction effects between p53 and iNOS have been reported, we hypothesized that iNOS activity in the thymus is causally linked to lymphomagenesis in Trp53-deficient mice. We therefore created mouse strains with different combinations of the Trp53 and iNOS genes. Western blot and histologic analyses showed that the iNOS protein was constitutively expressed in the thymus independently of Trp53 status and its expression was enhanced in Trp53+/- and Trp53-/- mice compared to Trp53+/+ mice. Homozygous disruption of iNOS decreased the incidence of thymic lymphomas by almost 40% (p=0.087) and 90% (p<0.05) in Trp53-/- and Trp53+/- mice, respectively, compared to the respective iNOS wild-type mice but significantly (p<0.05) increased the development of nonthymic lymphomas in Trp53-/- and Trp53+/- mice. Although iNOS gene disruption did not affect the phenotype of thymic lymphomas, absence of the iNOS gene shifted the spectrum of nonthymic lymphoma from the B-cell to the T-cell lineage. RT-PCR analysis revealed enhanced expression of IL-10, which could have a promoting effect on lymphomagenesis, even without any stimulation, in the spleen of aging mice with the gene combinations Trp53-/-iNOS-/- and Trp53+/-iNOS-/- but not Trp53-/-iNOS+/+ or Trp53+/-iNOS+/+. These results suggest that iNOS could increase the development of thymic lymphomas in Trp53-deficient mice. While iNOS may have protective effects against nonthymic lymphomagenesis, the regulation of cytokine production by iNOS may be involved in the underlying mechanism of antilymphomagenesis effects in the peripheral lymphoid organ.

Animals↗
PubMedDate not supplied

CD44 co-stimulates apoptosis in thymic lymphomas and T cell hybridomas.

Thymic lymphomas and hybridomas vary in their sensitivity to dexamethasone (DEX). Identical variance has been demonstrated in our laboratory for apoptosis of such cells by primary thymic epithelial cells or a cell line (TEC). We have also shown that apoptosis induced by TEC was partially mediated by TEC-derived glucocorticoids (GC). We studied the responses of various thymic lymphomas and hybridomas to TEC and DEX. Of these cells, PD1.6 and 2B4 were sensitive whereas B10 were relatively resistant to either inducer. In the present study we found that TEC and DEX synergize in inducing B10 cell apoptosis. B10 cells could also undergo apoptosis by TEC, conditional upon the presence of a TEC-sensitive cell (PD1.6 or 2B4). Contact between TEC and B10 was essential for apoptosis to occur. Thus, TEC may provide two signals, one mediated by GC and the other requiring cell to cell contact. We then analyzed the involvement of co-stimulatory or adhesion molecules in the TEC-induced apoptosis of thymic lymphoma cells. Soluble anti-CD44 antibodies but not anti-CD18, CD2 or CD28, inhibited TEC-induced apoptosis of PD1.6. Dimerization of CD44 by immobilized antibodies augmented DEX-induced apoptosis of all the lymphomas tested. CD44 cross-linkage up-regulated expression of the pro-apoptotic protein Bax, and down-regulated the anti-apoptotic protein, Bclx(L), in the presence of DEX. Taken together, the data suggest that CD44 enhances the apoptotic response of T lymphoma cells to DEX, and that CD44 modulates TEC-induced apoptosis of thymic lymphomas.

Animals↗
PubMedDate not supplied

[Primary thymic lymphomas].

INTRODUCTION: Primary thymic lymphomas (PTLs) are uncommon, and their prognosis is linked with early treatment. A review is carried out of this disease in our hospital in order to determine the best diagnostic-therapeutic management for these patients. MATERIAL AND METHODS: Ten LPTs--four Hodgkin's and six non-Hodgkin's (4 primary mediastinal B lymphomas [PMBLs] and 2 lymphoblastic T lymphomas [LTLs]--were reviewed. Most of the patients were females, with a mean age of 23 +/- 10 years. RESULTS: The initial diagnostic suspicion in the Hodgkin's lymphomas was thymoma in two cases and lymphoma in the other 2. All of them underwent surgery, including an intra-operative biopsy, which was completed with a thymectomy in the two in which thymoma was reported. They were treated with radio and chemotherapy. The response was partial in two cases, and treatment was completed with a bone marrow transplant (BMT) (one died and the other had active disease). The non-Hodgkin's lymphomas had large tumors and short evolution. All of them received surgery, with an intra-operative biopsy in four and a thymectomy in two. They were treated with chemotherapy, with associated radiotherapy in two. The response was total in three, with two recurring, who are in complete remission after a BMT. In the other three the response was partial. CONCLUSIONS: In a patient with thymic tumour with a preoperative or intraoperative study suspected of having a lymphoma, it is necessary to do a biopsy and not resective surgery, to avoid unnecessary resections and morbidity. PTLs are uncommon but aggressive, principally the non-Hodgkin's lymphomas. The main treatment is radio and chemotherapy, with associated bone marrow transplantation in selected cases.

Adolescent↗
PubMed1996

Role of radioadaptation on radiation-induced thymic lymphoma in mice.

Thymic lymphoma (TL) was observed in different stages of development in 46% of male mice (23/50) following exposure to an acute challenge dose of 2 Gy 60Co gamma-rays. With an adapting dose of 1 cGy 24 h prior to the challenge dose of 2 Gy, similar growth of TL was seen in 42.5% of mice (17/40). TL was not found in unirradiated control mice (0/50) or in the group treated with 1 cGy (0/50). Multiple adapting doses for 5 or 10 consecutive days induced TL in 8/50 and 9/50 mice, respectively (17% in average). When multiple adapting doses were followed by the challenge dose, the yield of TL was much lower, 16% (8/50) and 30% (15/50), respectively. By 15, 30, 60, 90, and 120 days after exposure with 3 Gy of 60Co gamma-rays, TL developed in 30, 70, 70, 80 and 85% of the female mice, respectively. When mice were conditioned with an adapting dose of 1 cGy 24 h prior to the challenge dose, TL was not found 15 days post-irradiation, while about a 25% reduction in the occurrence of TL was noticed at all other intervals. The results suggested that an adapting dose could play a role in bringing about a change in terms of delay and inhibition of the acute effects of radiation, i.e., the onset of TL in mice.

Adaptation, Physiological↗
PubMed2003

Impaired phosphorylation and mis-localization of Bub1 and BubR1 are responsible for the defective mitotic checkpoint function in Brca2-mutant thymic lymphomas.

Breast cancer susceptibility gene, BRCA2, is a tumor suppressor and individuals who inherit one defected copy of BRCA2 allele experience early onset breast cancer or ovarian cancer accompanied by the loss of the wild type allele. Mouse model for Brca2 mutation shows growth retardation and paradoxical occurrence of thymic lymphomas. Thymic lymphomas from Brca2-mutant mice harbor mutations in p53, Bub1, and BubR1, which function as mitotic checkpoint proteins. Therefore, interplay between Brca2 and mitotic checkpoint has been suggested in the maintenance of genetic fidelity, although it has not been assessed whether the unique mutations in Bub1 and BubR1 found in Brca2-mutant mice are responsible for the abolishment of mitotic checkpoint function. This report demonstrates that Bub1 and BubR1 mutant proteins from Brca2-/- thymic lymphomas have defects in the phosphorylation and kinetochore localization after spindle damage. Thus, the mutations of Bub1 and BubR1 found in Brca2- mutant mice indeed are responsible for the chromosome instability in Brca2-mutated tumors.

Animals↗
PubMed1986

Immunological and ultrastructural observations on swine thymic lymphoma.

A case of swine thymic lymphoma is described. A young pig had a mediastinal mass and bone marrow involvement and the microscopic findings showed peripheral blood involvement. The tumour was composed of small to medium sized lymphoid cells which formed rosettes with sheep erythrocytes and were characterized by narrow cytoplasmic bands, nuclear convolution and clustered dense bodies. Such structural and immunological features resembled those of human thymic lymphomas derived from thymic T-cells.

Animals↗
PubMed2004

Defective expression of Notch1 and Notch2 in connection to alterations of c-Myc and Ikaros in gamma-radiation-induced mouse thymic lymphomas.

Gamma-radiation-induced thymic lymphomas constitute a heterogeneous group of T-cell lymphomas. Some tumour suppressor genes and oncogenes have been shown to be defective in a fraction of such lymphomas, yet a considerable number of these remain elusive in terms of gene alterations. In the present work we present evidence that gamma-radiation-induced thymic lymphomas in (C57BL/6 J x BALB/c) F1 hybrid mice often exhibit increased levels of Notch1 expression, but, contrary to what was expected, they also exhibit a clearly reduced Notch2 mRNA expression, suggesting a cooperative antagonism of these genes. These results represent the first reported instance for the involvement of Notch2 inactivation in the development of thymic primary tumours while confirming the role of Notch1 as an activated oncogene. Additional analyses revealed that c-Myc over-expression and partial inactivation of Znfn1a1/Ikaros appear to be relevant events some how coupled to alterations in Notch genes inducing these kinds of tumours.

Animals↗
PubMed2005

Comparison of properties of spontaneous and radiation-induced mouse thymic lymphomas: role of Trp53 and radiation.

Mouse thymic lymphomas are readily induced by radiation and also arise without irradiation when the mice are null in Trp53 functions. In the present study, spontaneous thymic lymphomas in Trp53-/- mice were compared to those arising in irradiated Trp53+/- mice, revealing three features characteristic of the spontaneous lymphomas. (1) Mp53D2, a Trp53 modifier that affects the latent period of radiogenic thymic lymphomas in Trp53+/- mice, had no effect on the development of spontaneous lymphomas. (2) A sex difference in the latency was found. (3) A marked difference was noted in the frequency of allelic loss at the Ikaros gene on chromosome 11, encoding a transcription factor required for normal lymphocyte development and differentiation; 2% in the lymphomas of Trp53-/- mice and 78% in the radiogenic lymphomas of Trp53+/- mice, suggesting that loss of Trp53 may reduce the requirement for the loss of Ikaros for lymphomagenesis. Furthermore, allelic loss analysis on chromosome 19 localized a region that may harbor an unknown tumor suppressor gene. These results suggest intricate steps of lymphomagenesis influenced by the presence or absence of Trp53.

Animals↗
PubMed2004

Control of Atm-/- thymic lymphoma cell proliferation in vitro and in vivo by dexamethasone.

AIM: Ataxia telangiectasia (A-T) is an autosomal recessive disease in humans caused by mutations in the Atm (A-T mutated) gene. The disease involves multiple organ systems, and is associated with a high incidence of leukemias and lymphomas that develop in childhood. We have reported previously that thymic lymphoma development in Atm knockout (Atm-/-) mice is associated with elevated spontaneous DNA synthesis in thymocytes, and that dexamethasone (Dex) attenuates the elevated DNA synthesis and prevents thymic lymphoma development. The primary objectives of the present study were (1) to investigate possible mechanisms underlying the tumor-suppressing effect of Dex on Atm-/- thymic lymphoma cells, and (2) to determine whether Dex is an effective tumor-suppressing treatment in mice bearing transplanted Atm-/- thymic tumors. METHODS: Establishment of a number of Atm-/- thymic lymphoma (ATL) cell lines from Atm-/- mice, cell proliferation assays, cell cycle analyses, Western blotting and Hoechst nuclear staining were used to analyze the effects of Dex on Atm-/- thymic lymphoma cells. Atm-/- tumor cells were transplanted into the right flanks of Atm+/+ mice prior to the initiation of Dex treatment. RESULTS: Atm-/- tumor cells were highly sensitive to Dex, both in culture and in vivo as ectopic tumors in mice. In cultured ATL-1 cells, Dex induced apoptosis, arrested the cell cycle at the G1 phase and downregulated NF-kappaB and multiple cell cycle regulators, while upregulating the NF-kappaB inhibitor IkappaBalpha. In Atm+/+ mice transplanted subcutaneously with ATL-1 cells, tumor growth was either prevented completely or significantly suppressed by Dex treatment. CONCLUSIONS: Our findings identify potential mechanisms by which Dex affects the proliferation and survival of ATL-1 cells in culture, and provide evidence that Dex can suppress the proliferation of Atm-/- thymic lymphoma cells growing in the body. Together these results add to our earlier published data suggesting that the cellular pathways regulated by Dex may be promising therapeutic targets for prevention and treatment of thymic lymphomas in A-T individuals.

Animals↗
PubMed1985

Genetically determined susceptibility of Fischer 344 rats to propylnitrosourea-induced thymic lymphomas.

Administration of propylnitrosourea p.o. by our protocol induced a high incidence of hematolymphatic neoplasms in all six rat strains studied. Remarkable strain differences in susceptibility to thymic lymphomas were observed. The incidence of thymic lymphomas was high in Fischer 344 (98%) and Wistar/Furth (71%) but low in Sprague-Dawley (29%), ACI/Ms (23%), Donryu (24%), and Long-Evans (10%) strains. Segregation of thymic lymphoma incidence among crosses between highly susceptible Fischer and poorly susceptible Long-Evans rats indicated that the increased susceptibility to thymic lymphomas of Fischer rats was determined by a dominant gene TIs-1 (thymic lymphoma susceptible) and that this gene was linked to the coat color loci, p and c, in Linkage Group I in the order of TIs-1 - c - p. The presence of another independently assorting dominant gene, TIs-2, was also suggested to accelerate the thymic lymphoma-genesis. Expression of the group-specific antigen of murine leukemia virus as well as infectious viruses was not detected in nine propylnitrosourea-induced thymic lymphomas of Fischer rats.

Animals↗