The S-phase-dependent radioresistance to killing uniformly seen in eukaryotic cells is absent in radiosensitive mutants with defects in genes involved in the repair of DNA double-strand breaks (DSBs) by homologous recombination (homologous recombination repair: HRR). This implicates, for the first time, a concrete DNA repair process in the radiosensitivity of a specific cell cycle phase. The cell cycle-dependent fluctuations in radiosensitivity reflect a fundamental and well-documented radiobiological phenomenon that still awaits a detailed molecular characterization. The underlying mechanisms are likely to combine aspects of DNA repair and cell cycle regulation. Advances in both fields allow a first dissection in the cell cycle of the molecular interplay between DSB repair and DNA damage checkpoint response and its contribution to cell survival. Here we review the available literature on the topic, speculate on the ramifications of this information for our understanding of cellular responses to DNA damage, and discuss future directions in research. An effort is made to integrate relevant phenomena of radiation action, such as low-dose radiosensitivity and the G(2) assay in this scheme.
The development of metabolic imaging in normal or tumour tissue sections using bioluminescence detection makes it possible to study the relation between their histology and the spatial distribution of metabolites, e.g. ATP, glucose and lactate. Previous method usng photographic film for imaging these metabolites in normal brain and tumour sections (Hossmann et al., 1986;Paschen, 1990) were often very time consuming and not always reproducible owing to the poor resolution obtained. This drawback has been largly overcome through the introduction of high resolution single photon imaging (Muller-Kiieser et al., 1988), to the ectent that metabolite levels can be quantified in absolute values. This technique has clearly demonstrated that metabolites are distributed much more heterogeneously in tumours than in normal tissues, where the pattern is of a more homogeneous nature. This finding is not unexpected in view of the chaotic vasculature frequently seen within tumours (Konerding et al., 1989a, b). As a result, solid tumours often show areas with a restric blood perfusion and poor nutritve supply. Such regional differences may be of relevance to radiobioogical hypoxia in viable tumour areas. In addition, the use of biolumiescence can help to distinguish between viable and necrotic regions in tumours not possible with other conventional biochemical techniques. Such methods produce only average values for the whole tissue in question and are unable to give details as to their spatial distribution in the regions of interest or 'hotspots'.Since ghlcs metabolism is very important for energy production in tumours (Streffer, 1994), it was of interest to investigate possible correlations between the distribution of ghluose, lactate and ATP in a number of different tumour entities, including a squamous head and neck carcnoma, a melanoma, a rectum carcinoma and a murine mammary adenocarcinoma maintained as xenotransplants on nude mice using the novel methodology of photon imaging. We compared the metabolic distributions in cryosections from these xenotransplants with those in normal heart muscle.
Materls aud mhodsTwnours All tumours were maintained as xenografts on nude mice (NMRI strain) as described previously (Steinberg et al.,
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