RESUMO
A new set of rat RI strains consisting of 11 independent strains and 13 of their substrains was established by inbreeding F2 rats between F344/DuCrj and LE/Stm. The strain distribution pattern was examined for 66 microsatellite loci, 8 biochemical genetic markers, 2 histocompatibility loci, and 2 coat color genes. A rat salivary protein gene Spe1 was newly mapped on Chr 1.
Assuntos
Ratos Endogâmicos F344/genética , Ratos Endogâmicos/genética , Alelos , Animais , Mapeamento Cromossômico , Feminino , Marcadores Genéticos , Cor de Cabelo/genética , Masculino , Repetições de Microssatélites , Ratos , Recombinação Genética , Proteínas e Peptídeos Salivares/genética , Especificidade da EspécieRESUMO
In situ estimation of DNA fragmentation by the nick end labelling (NEL) method, and immunohistochemical examination of Ki-67 proliferative antigen and bcl-2 products in human endometrial adenocarcinoma tissues were performed to provide answers to the following two questions; a) does apoptotic DNA fragmentation occur specifically in quiescent cells or in proliferating cells or randomly in both?, b) does the bcl-2 product exert its apoptosis-suppressing effects differentially on carcinoma cells depending on their cell cycle condition?. Serial sections, one micrometer in thickness, from formalin-fixed and paraffinembedded tissues of 9 cases of human endometrial adenocarcinoma were examined. Apoptotic DNA fragmentation was observed in both quiescent (Ki-67 negative) and proliferating (Ki-67 positive) cells. Bcl-2 product-positive tumor cell islands tended to be NEL negative, although a few but non-negligible number of carcinoma cells, including both Ki-67 positive and negative ones, were NEL positive. These results indicate that, at least in human endometrial adenocarcinomas, apoptotic DNA fragmentation and bcl-2 product-independent (DNA) fragmentation occurs non-specifically with respect to the cell proliferation status. Further, the results suggest an altered regulation of cell death processes in human solid tumor tissue in vivo.
Assuntos
Fragmentação do DNA , DNA de Neoplasias , Neoplasias do Endométrio/genética , Proteínas de Neoplasias/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Idoso , Ciclo Celular , Divisão Celular , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
In situ estimation of DNA fragmentation by the nick end labeling method and immunohistochemical detection of cell surface carbohydrate Le(y) were performed to establish correlation between the results of these two apoptosis-detecting techniques in human solid tumor tissues. Formalin-fixed and paraffin-embedded tissue samples from 10 cases of human endometrial adenocarcinoma were examined and compared by using the two techniques. A substantial fraction of carcinoma cells was found to be definitely stained by both methods, although Le(y) expression did not seem to be positively correlated with DNA fragmentation in the carcinoma tissue. These results suggest that Le(y) expression does not necessarily reflect apoptotic DNA fragmentation, at least in human endometrial adenocarcinomas, and simultaneous application of DNA nick end labeling and Le(y) immunostaining is necessary to show the relevant signs of apoptosis in histologic slides, especially gynecological cancers.
Assuntos
Fragmentação do DNA , DNA de Neoplasias/análise , Neoplasias do Endométrio/genética , Antígenos do Grupo Sanguíneo de Lewis/análise , Neoplasias do Endométrio/patologia , Feminino , HumanosRESUMO
Immunohistochemical detection of bcl-2 products and in situ estimation of DNA fragmentation during apoptosis by the nick and labelling method were performed to establish any correlation between these two apparently opposing processes in human solid tumors. Serial sections, one micrometer in thickness, from formalin-fixed and paraffin-embedded tissues of 10 cases of human endometrial adenocarcinoma were examined using the two techniques. A significant fraction of carcinoma cells were found to be stained by both methods, although there existed a general tendency for bcl-2 expression to be negatively correlated with DNA fragmentation in carcinoma tissue. The results thus suggest that bcl-2 expression does not always block apoptosis, and that simultaneous application of bcl-2 immunostaining and DNA nick end labeling is useful for showing the complex nature of apoptosis in histologic slides, especially in gynecological cancers.
Assuntos
Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Fragmentação do DNA , DNA de Neoplasias/genética , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Idoso , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
The murine spontaneous B lymphoma is etiologically related to the expression of endogenous ecotropic murine leukemia virus (ETV). Although both SL/Kh and SL/Ni mouse strains show a high level of expression of ETV from early in life, the former is a pre-B lymphoma-prone strain and the latter is rather lymphoma-resistant. In order to identify the host background difference related to the lymphomagenesis, we performed a genetic cross study between these two strains. In the reciprocal F1 generation, the length of the lymphoma latent period was slightly but significantly longer in (SL/Ni xSL/Kh)F1 than in (SL/KhxSL/Ni)F1(P < 0.05). The incidence of overall lymphomas and that of acute pre-B lymphomas was lower in (SL/NixSL/Kh)F1 than in (SL/KhxSL/Ni)F1, although the difference was not statistically significant. These observations indicate that an epigenetic maternal resistance mechanism of SL/Ni mice plays a role in the lymphoma resistance. Furthermore, in the backcross combinations without maternal influence of SL/Ni, we observed a genetic mechanism of lymphoma resistance: an SL/Ni-derived recessive lymphoma-resistance gene mapped in the proximal segment of Chr. 4. We named this gene nir-1 (SL/Ni-lymphoma resistance-1). Thus, we have demonstrated epigenetic and genetic mechanisms of lymphoma resistance of the SL/Ni mouse with the high expression of endogenous ETV.
Assuntos
Impressão Genômica , Vírus da Leucemia Murina/patogenicidade , Linfoma de Células B/genética , Camundongos Endogâmicos/genética , Animais , Cruzamentos Genéticos , Feminino , Regulação Neoplásica da Expressão Gênica , Regulação Viral da Expressão Gênica , Genes Recessivos , Ligação Genética , Predisposição Genética para Doença , Imunidade Inata/genética , Imunidade Materno-Adquirida , Vírus da Leucemia Murina/genética , Vírus da Leucemia Murina/fisiologia , Linfoma de Células B/virologia , Masculino , Camundongos , Camundongos Endogâmicos/virologia , Repetições de Microssatélites , Leite/imunologia , Provírus/genética , Baço/virologia , Replicação ViralRESUMO
Susceptibility to T lymphomas in mice is determined by a number of viral and host genetic factors. We analyzed the types and latent period of lymphomas spontaneously occurring in crosses between AKR/Ms, a T lymphoma-prone mouse strain, and SL/Kh, a pre-B lymphoma-prone strain. The incidence of T lymphomas in the F1 hybrids backcross to SL/Kh as well as F2 generation mice indicated that a dominant host gene thymic lymphoma susceptible mouse-1 (Tlsm-1) of AKR/Ms determined the type of lymphomas to be thymic. Linkage analysis with microsatellite markers assigned Tlsm-1 to the map position 61 cM from centromere of the chromosome 7. Close scrutiny of this region of AKXD recombinant inbred strains for spontaneous T lymphomas revealed the presence of Tlsm-1-like gene most likely between D7MIT71 (map position 62) and D7MIT13 (map position 70). On the other hand, a SL/Kh-derived recessive allele at a major histocompatibility complex (MHC)-linked locus accelerated development of both T and B lymphomas.