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  • Title: Fibroblasts from patients with inherited predisposition to retinoblastoma exhibit normal sensitivity to the mutagenic effects of ionizing radiation.
    Author: Wang Y, Parks WC, Wigle JC, Maher VM, McCormick JJ.
    Journal: Mutat Res; 1986 Oct; 175(2):107-14. PubMed ID: 3762576.
    Abstract:
    Retinoblastoma (RB) is a cancer of the retina which characteristically occurs in early childhood. Bilateral RB is an inherited form of this disease. Such patients are at greatly increased risk of subsequently developing second tumors in mesenchymal tissue, especially in areas exposed to ionizing radiation therapy. Fibroblasts from bilateral RB patients have been reported to be more sensitive than normal fibroblasts to the cytotoxic effects of ionizing radiation. Because xeroderma pigmentosum patients have a hereditary predisposition to UV-induced cancer and the cells of such patients are abnormally sensitive to the cytotoxic and mutagenic effects of UV radiation, we compared fibroblasts from 6 bilateral RB patients and 3 normal individuals for their sensitivity to the mutagenic effects of cobalt 60, using resistance to 6-thioguanine (TG) as the genetic marker. The results showed no statistically significant difference between the two types of cell lines. The slope of the weighted least squares line representing the frequency of TG-resistant cells induced in the RB populations as a function of dose was 17 +/- 6 (S.E.)/10(6) cells/Gy with an intercept of 0.09 Gy; that for the normal cells was 17 +/- 7/10(6) cells/Gy with an intercept of 0.14 Gy. We also compared 8 bilateral RB cell lines and 9 age-matched normal cell lines for their sensitivity to the cytotoxic effect of 60Co, using survival of colony-forming ability. The cloning efficiency of the unirradiated RB cell lines ranged from 22% to 76% with an average of 52%; that of the normal cell lines from 21% to 89% with an average of 64%. The results showed the RB cells were somewhat more sensitive than the normal cells. The mean D0 for the RB cell lines ranged from 0.99 +/- 0.01 (S.E.) to 1.69 +/- 0.04 Gy with a weighted average of 1.44 +/- 0.08 Gy; that of the normal cell lines ranged from 1.42 +/- 0.17 to 2.24 +/- 0.10 Gy, with a weighted average of 1.79 +/- 0.11 Gy. The difference in means was estimated to be 0.34 +/- 0.14. The mean for the RB cell lines is statistically significantly lower than the mean for the normal cell lines, at a significance level ca. 1%.
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