PubMed · 8618733
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K Landau, H E Killer. 1996. Radiation damage.. https://pubmed.ncbi.nlm.nih.gov/8618733/
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The high mobility group As (HMGAs) belong to a family of nonhistone nuclear proteins that orchestrate the assembly of nucleoprotein complexes. Through a complex network of protein-DNA and protein-protein interaction, they play important roles in gene transcription, recombination, and chromatin structure. This protein family is involved, through different mechanisms, in both benign and malignant neoplasias. We have recently reported that transgenic mice carrying the Hmga1 or Hmga2 genes under transcriptional control of the cytomegalovirus promoter develop pituitary adenomas secreting prolactin and growth hormone. We have shown that the mechanism of the HMGA2-induced pituitary adenoma is based on the increased E2F1 activity. The expression profile of mouse normal pituitary glands and adenomas induced in HMGA transgenic mice revealed an increased expression of the ccnb2 gene, coding for the cyclin B2 protein, in the neoplastic tissues compared with the normal pituitary gland. Here, we show, by electrophoretic mobility shift assay and chromatin immunoprecipitation, a direct binding of HMGA proteins to the promoter of ccnb2 gene, whereas luciferase assays showed that HMGAs are able to up-regulate ccnb2 promoter activity. Finally, we report an increased CCNB2 expression in human pituitary adenomas of different histotypes that is directly correlated with HMGA1 and HMGA2 expression. Because cyclin B2 is involved in the regulation of the cell cycle, these results taken together indicate that HMGA-induced cyclin B2 overexpression gives an important contribution to experimental and human pituitary tumorigenesis.
PURPOSE: By using cell survival as a reference, we evaluated the radiosensitivity of human normal and tumoral thyroid cells using of radiation-induced translocations. METHODS AND MATERIALS: Tissue samples were obtained from patients undergoing thyroidectomy. Cell cultures were established, irradiated with 60Co, and metaphases painted using commercial whole-chromosome 4 hybridization probe and pancentromeric probe. The clonogenic survival was assessed by conventional colony forming assay. RESULTS: After irradiation, normal cultured thyroid cells yielded a higher number of translocations than cultures derived from adenomas or thyroid carcinoma. The colony forming assay demonstrated, by way of the mean inactivation dose, a higher survival of thyroid carcinoma and adenoma cells than of normal thyroid cells. This difference between tumoral and nontumoral cells is significant in each method (p = 0.0001), and cannot be explained by apoptosis in irradiated malignant cells. Correlation of the results obtained by both methods is shown by comparing the survival fraction at 2 Gy (SF2) and the percentage of chromosome 4 translocations at 2 Gy. CONCLUSION: These results indicate that the yield of radiation-induced translocations serves as a good and rapid prediction of the intrinsic radiosensitivity of thyroid cells, and that this test could be applied to other tumors.
Bile acids are important in the etiology of colorectal cancer. Bile acids induce apoptosis in colonic goblet cells at concentrations comparable to those found in fecal water after high-fat meals. Preliminary evidence indicated that cells of the normal-appearing (nontumorous) portion of the colon epithelium of colon cancer patients are more resistant to bile salt-induced apoptosis than are cells from normal individuals. In the present study, 68 patients were examined, and biopsies were taken at 20 cm from the anal verge, cecum, and descending colon. The patients included 17 individuals with a history of colorectal cancer, 37 individuals with adenomas, and 14 individuals who were neoplasia free. The mean bile salt-induced apoptotic index among normal individuals was 57.6 +/- 3.47 (SE), which differed significantly (P < 0.05) from the mean value of 36.41 +/- 3.12 in individuals with a history of colon cancer. The correlation between independent observers was 0.89 (P < 0.001), indicating good interobserver reliability. Components of variance comparing interindividual versus intraindividual sources of variation suggested that site-to-site variability, both between regions of the colon and for adjacent biopsies, was larger than the interpatient variability for individuals with a history of neoplasia. Therefore, there was "patchiness" of the susceptibility of regions of the colon to bile acid-induced apoptosis in individuals with a history of neoplasia (a patchy field effect). There was no obvious correlation of low-apoptotic index regions with regions in which previous neoplasias had been found and removed. On the other hand, for normal, i.e., neoplasia-free, individuals, there was relatively less intraindividual variation compared to interindividual variation. Our assay shows an association between resistance to bile acid-induced apoptosis, measured at 20 cm from the anal verge, and colon cancer risk. Thus, this assay may prove useful as a biomarker of colon cancer risk.