Ataxia-telangiectasia: a human genetic disorder with predisposition to cancer.
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Biomedical subjects
Publications and source records attributed to M Lavin.
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The resistance of a human melanoma cell line (MM96) to both ultraviolet and ionizing irradiation was compared by two different methods of cloning, on plates and in agar. A high level of resistance to both ultraviolet (D0 = 320 ergs/sq mm) and ionizing irradiation (D0 = 4300 rads) was observed when viability of cells was determined by cloning in agar. In contrast, melanoma cells were found to be as sensitive as were other cells when viability after irradiation was determined by cloning on plastic plates. The difference in sensitivity to radiation between the two methods of cloning can be explained in a model involving damage to membranes as well as to DNA. At least for ionizing radiation, this effect is not restricted to melanoma cells since a HeLa subline, HeLa-QB1, showed a similar response. In contrast, a human lymphoblastoid line (JHP) cloned in agar was sensitive under these conditions (D0 = 120 rads).
Mouse neuroblastoma cells, which can be induced to undergo reversible differentiation in culture, have been used as a model to investigate the effects of ultra-violet (U.V.) radiation on terminally-differentiated nerve cells. Differentiated neuroblastoma cells were found to be extremely sensitive to U.V.-radiation when compared with proliferating cells from the same clone. However, normal resistance was regained if the differentiated cells were allowed to proceed to the next G1 phase of the cell-cycle before irradiation. Neuroblastoma cells in the differentiated mode are capable of carrying out soem excision repair of DNA damage, but they appear to lack a repair mechanism present in proliferating cells.
A series of five human melanoma cell lines has been demonstrated to be highly resistant to ultraviolet (UV) radiation, with a D0 of 400 ergs/sq mm. Melanotic melanoma cells were found to increase their production of melanin following UV radiation, whereas some amelanotic cells did not. Melanotic and amelanotic melanoma cell lines exhibited the same UV resistance; melanoma and nonmelanoma cells formed the same numbers of thymine dimers at a given UV dose. These data imply that melanin does not play a major role in protecting DNA of melanoma cells against UV damage in culture. The rates of removal of thymine dimers from DNA of melanoma cells were comparable to those in UV-sensitive, nonmelanoma cell lines, so that rapid excision repair does not explain UV resistnace in the melanoma cells. No DNA strand breakage was detected in a melanoma cell line at moderate UV doses.
Human melanoma cells are highly resistant to 254-nm light. Resistance appears to depend on their ability to continue replication after high UV doses due to the presence of a very efficient postreplication repair system, while excision-repair is of relatively minor importance.
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Explore the source record for details and available documents.