G2 radiosensitivity of cells derived from cancer-prone individuals.
The potential of enhanced chromatid damage, observed after X-irradiation of G2 phase, has been used to detect individuals genetically predisposed to cancer, utilising fibroblast/lymphocytes from these patients as well as fibroblasts derived from human tumours. Fibroblasts and/or lymphocyte samples of two autosomal recessive syndromes (xeroderma pigmentosum (XP), Fanconi's anaemia (FA)) and one congenital or acquired disorder, aplastic anaemia (AA), were employed for the G2 radiosensitivity assay. In addition, we have estimated the frequencies of spontaneously occurring chromosomal aberrations as well as G2 radiosensitivity of eight samples of fibroblasts/fibroblast-like cells (two normal, two colorectal carcinoma, two Wilms' tumour, one retinoblastoma and one polyposis coli), and three samples of lymphocytes (two normal and one from a lymphoma patient). The results obtained indicate that there were no differences between fibroblast cells derived from patients or tumours, except FA patients, in the frequency of spontaneously occurring chromosomal aberrations when compared to normal cells. Following X-irradiation we did not observe any significantly increased G2 radiosensitivity in FA and XP cells. Lymphocytes from AA and lymphoma patients, and all tumour cell lines except retinoblastoma, responded with increased frequencies of aberrations following G2 X-irradiation in comparison to cells derived from normal individuals. In our hands, the G2 sensitivity assay could not always discriminate cells from cancer-prone individuals from those of controls.
Darroudi
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Department of Radiation Genetics and Chemical Mutagenesis, State University of Leiden, The Netherlands.
Vyas
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Vermeulen
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Natarajan
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D011125:Adenomatous Polyposis Coli / Q000503:physiopathology; D000741:Anemia, Aplastic / Q000503:physiopathology; D002842:Chromatids / Q000528:radiation effects*; D002869:Chromosome Aberrations; D015179:Colorectal Neoplasms / Q000503:physiopathology; D004198:Disease Susceptibility; D005199:Fanconi Anemia / Q000503:physiopathology; D005347:Fibroblasts / Q000528:radiation effects; D016195:G2 Phase / Q000528:radiation effects*; D006801:Humans; D008214:Lymphocytes / Q000528:radiation effects; D009369:Neoplasms / Q000235:genetics*; D011836:Radiation Tolerance; D012175:Retinoblastoma / Q000503:physiopathology; D014407:Tumor Cells, Cultured / Q000528:radiation effects; D009396:Wilms Tumor / Q000503:physiopathology; D014983:Xeroderma Pigmentosum / Q000503:physiopathology