The mechanisms by which the p53 tumour suppressor protein would, in vivo, co-ordinate the adaptive response to genotoxic stress is poorly understood. p53 has been shown to transactivate several genes that could be involved in two main cellular responses, growth arrest and apoptosis. To get further insight into the tissuespeci®c regulation of p53 transcriptional activity, we performed an extensive study looking at the expression of four well characterized p53-responsive genes, before and after g-irradiation in p53 wild-type (p53+/+) and p53-de®cient (p537/7) mice. The waf1, bax, fas and mdm2 genes were chosen for their dierent potential roles in the cellular response to stress. Our data demonstrate the strict p53-dependence of mRNA upregulation for bax, fas and mdm2 in irradiated tissues and con®rm such ®ndings for waf1. They further highlight complex levels of regulatory mechanisms that could lead, in vivo, to selective transcriptional activation of genes by p53. In addition, our results provide arguments for the involvement of p53 in the basal mRNA expression of the four genes in some organs. Finally, in situ expression of Bax and p21Waf-1 protein suggests, at least in lymphoid organs, a direct correlation between selective p53-target gene expression and a particular response of a cell to ionising radiation.

Two forms of linear DNAs have been found in simian (SFV1) and human (HSRV) spumaviruses: a linear duplex unsensitive to nuclease S1 and a sensitive structure with a single-stranded gap. Two nuclease S1 sensitive sites, mapping at the same position for both viruses, have been identified in the gapped structure. Using different molecular subgenomic clones of HSRV as probes in Southern blot analysis, one S1 site was localized in the 3'LTR and the other near the middle of the molecule at about 6.5 kbp from the 5' end of the viral genome. The latter site was shown to correspond to a single stranded region within the linear duplex DNA. Nucleotide sequence analysis revealed that the polypurine tract (PPT) usually found at the 5' boundary of the 3'LTR of retroviruses, is duplicated in HSRV at the 3' end of the pol gene, near the gap. This suggests that the synthesis of plus strand DNA is discontinuous, generating the gap.

Viruses, and more particularly retroviruses, have been postulated to play a role in the pathogenesis of autoimmune diseases. In a search for spumaretrovirus infection markers, we screened a group of 29 patients with Graves disease and a representative healthy population (23 subjects) as a control. Southern blot hybridization under s ent conditions, of patients' DNA extracted from peripheral blood lymphocyes, with a spumaretrovirus-specific genomic probe derived from the human spumaretroirus (HSRV) prototype, gave a positive signal in 10 cases. Moreover, by PCR, HSRVrelated sequences were detected in the DNA of 19 patients (66%). Positive DNA samples in Southern blots were also positive in PCR for all regions tested (gag, bell, li2, long terminal repeat). Amplified (gag and bel2) products were cloned and sequenced; they showed hih homology with HSRV. On the other hand, all 23 control subjects were negative by both procedures. Sera from both populations were ex for the presence of antibodies reactive with antigens of the spumaretrovirus family. These sera were negative by several immunodetection techniques: ELISA, indirect immunofluorescence, serum neutralization, and Western blotting. These results strongly suggest the existence of an assoclation between Graves disease and the presence of HSRV-related infection markers.Several clinical, genetic, and pathophysiological features support the notion of a role for autoimmunity in the pathogenesis of some endocrine conditions, such as Graves disease. In fact, the association of this affliction with other well-defined autoimmune nosological eptities-altered HLA expression, the. presence of autoantibodies, and modifications of certain lymphocyte subpopulations-favor this concept (1, 2).The possible involvement of different viruses in the etiology of autoimmune diseases has been evoked in animal models and in humans. Among viral agents, endogenous (3) and exogenous (4-6; §) retroviruses have been considered as likely candidates to be associated with this category of disorders. Animal models have produced evidence sustaining this hypothesis. For instance, in the genome of the obese chicken, which spontaneously develops autoimmune thyroiditis, an avian leukosis virus (ev22) has been identified (3). Moreover, type C retroviral particles have been detected in