Hamatologie und Bluttransfusion最新文献

The tissue specificity of Moloney leukemia virus (M-MuLV) was studied by infecting mice at two different stages of development. Either newborn mice which can be considered as essentially fully differentiated animals were infected with M-MuLV or preimplantation mouse embryos were infected in vitro at the 4-8 cell stage, a stage of development before any differentiation has taken place. After surgical transfer to the uteri of pseudopregnant surrogate mothers, the latter developed to term and adult mice. In both cases, animals were obtained that had developed an M-MuLV induced leukemia. Molecular hybridization tests for the presence of M-MuLV-specific sequences were conducted on DNA extracted from different tissues of leukemic animals to determine which tissues were successfully infected by the virus. Mice which were infected as newborns carried M-MuLV-specific DNA sequences in "target tissues" only, i. e., thymus, spleen, lymph nodes or in organs infiltrated by tumor cells, whereas "non-target tissues" did not carry virus-specific sequences. In contrast, when leukemic animals derived from M-MuLV-infected preimplantation embryos were analyzed, virus-specific sequences were detected in target tissues as well as in non-target tissues, such as liver, kidney, brain, testes and the germ line. To study the expression of the viral DNA integrated in target and non-target organs, RNA was extracted from different tissues of an animal infected at the preimplantation stage. Fifty to 100 times more M-MuLV-specific RNA was detected in tumor tissues than was found in non-target organs. Since all organs contained the same amount of virus-specific DNA, these results indicate that the integrated virus genome can be differentially expressed in different tissues. The organ-tropism of RNA tumor viruses is discussed in view of these findings. Mice that were infected at the preimplantation stage were found to have M-MuLV integrated into their germ line. Virus transmission from the father to the offspring occurred according to simple Mendelian expectations. Molecular hybridization tests revealed that in the animals studied, the virus was integrated into the germ line at only one out of two or three possible integration sites. During the development of leukemia amplification of this virus copy was observed in the target tissues only, but not in the non-target tissues.

Initiation of protein synthesis in tissue culture cells is rapidly inhibited or blocked by addition of either DMSO, ethanol, TPCK, cytochalasin B, or sucrose to the growth medium. In contrast, these agents do not interfere with the initiation of protein synthesis in cell-free extracts to a comparable extent. These results support the hypothesis that protein synthesis in tissue culture cells can be influenced by membrane mediated events. Translation of viral mRNA in RNA virus infected cells is resistant to a number of these inhibitors of peptide chain initiation and proceeds under conditions where translation of host mRNA is almost completely suppressed. It appears that viral mRNA possesses a greater ability than host mRNA to form mRNA-ribosome initiation complexes when the overall rate of peptide chain initiation is reduced. This observation has led to a number of predictions concerning the strategy of virus directed suppression of host mRNA translation. Under optimal growth conditions protein synthesis appears to be regulated mainly, but not exclusively, by the amount of the mRNA available for translation. However, when cellular growth and/or the overall rate of peptide chain initiation is restricted, control of protein synthesis at the translational level becomes decisive with the translation of each mRNA species proceeding with its own characteristic efficiency most probably as a result of inherent differential affinities of individual mRNA species for ribosomes.