Radiation Effects Research Foundation five year strategic research plan and program management, 1997-2001 Page: 78 of 152
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3263 It was observed in the recent somatic mutation study that the GPA mutation frequencies
3264 increased with increasing A-bomb radiation doses, and the dose-response curve is very
3265 similar to that for solid tumor incidence among the A-bomb survivors. We can expect that
3266 since radiation may cause DNA damage randomly in the cell, cancer-related gene
3267 alteration could have been induced and remained in the cells of the A-bomb survivors.
3268 Based on the multi-step carcinogenesis theory, it may be suspected that cells carrying
3269 cancer-related gene alterations and proteins exist in blood cells among the A-bomb
3270 survivors.-
3271-
3272 A-1. Detection of the cells carrying mutations
3273
3274 Recent advances in flow cytometry make it possible to analyze translocation of cancer-
3275 associated genes by in-cell PCR methods using fluorescent primers. BCR-ABL and Bcl2
3276 translocations are both associated with blood malignancies and can be detected in G
3277 peripheral blood lymphocytes by this method.
3278
3279 Newly developed antibodies against oncogenes and tumor suppressor gene products will
3280 be used to detect cells carrying cancer-associated gene alterations in the blood among A-
3281 bomb survivors. This technique can demonstrate the existence of mutant gene products
3282 or changes in levels of normal gene products which may be especially pertinent in cases
3283 of deletion of tumor suppressor genes like p53 and possibly the ataxia telangiectasia
3284 mutated (ATM) gene. The projected number of samples to be studied is a 300 (control
3285 and high risk group). These approaches could provide meaningful information for
3286 understanding the molecular mechanisms of human radiation carcinogenesis and cancer
3287 risk estimation.
3288 f
3289 Special research activities (Molecular oncology)
3290
3291 Priority 1
3292 =
3293 B. Human radiation carcinogenesis (RP 18-81):
3294
3295 Strategically, not only are studies directly looking at tissues from the A-bomb survivors
3296 important, but studies taking advantage of experimental models could be very helpful in
3297 interpreting effects on the survivors. In the experimental system we have developed, we
3298 can examine the first and consequent events occurring in the cell at the cellular and
3299 molecular levels which may have crucial roles in human carcinogenesis.
3300
3301 B-1. Models
3302
3303 The severe combined immunodeficient (SCID) mouse-human chimera makes it possible
3304 to study radiation effects on humans in vivo, and thereby provide more relevant and
3305 meaningful information than those obtained in vitro or from other non-human animal
3306 models. We have already established a transplantation system of normal human tissues
3307 (skin, intestine, thyroid and bone marrow) to SCID mice which preserves in situ histology,
3308 structure and function. These models will be improved so that they are as close to the 2
3309 human situation as possible and will be applied to the studies on radiation response (see :71
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Radiation Effects Research Foundation five year strategic research plan and program management, 1997-2001, report, October 31, 1997; Washington D.C.. (https://digital.library.unt.edu/ark:/67531/metadc716813/m1/78/: accessed July 16, 2024), University of North Texas Libraries, UNT Digital Library, https://digital.library.unt.edu; crediting UNT Libraries Government Documents Department.