Teo I A, Broughton B C, Day R S, James M R, Karran P, Mayne L V, Lehmann A R
Carcinogenesis. 1983;4(5):559-64. doi: 10.1093/carcin/4.5.559.
The fibroblast cell strain 46BR, derived from an immunodeficient individual, is hypersensitive to the lethal effects of a variety of DNA-damaging agents, this effect being particularly marked for monofunctional methylating agents. After u.v. irradiation 46BR cells show normal unscheduled DNA synthesis, daughter strand repair, and recovery of DNA and RNA synthesis. The inhibition of DNA replicative synthesis by u.v. is slightly less than that of normal cells. After gamma-irradiation the rejoining of strand breaks is normal as are the kinetics of replicative DNA synthesis. Following treatment with dimethylsulphate, replicative DNA synthesis is affected in a similar way to normal cells, unscheduled DNA synthesis may be increased relative to normal cells, but more strand breaks persist in 46BR than in normal cells. In addition 46BR cells are hypersensitive to the toxic effects of 3-aminobenzamide, an inhibitor of ADP-ribosyl transferase. This enzyme is involved in the ligation step of repair of alkylation damage. A hypothesis is presented suggesting that 46BR may be defective in DNA ligase I.
源自一名免疫缺陷个体的成纤维细胞系46BR，对多种DNA损伤剂的致死效应高度敏感，这种效应在单功能甲基化剂中尤为明显。紫外线照射后，46BR细胞表现出正常的非预定DNA合成、子链修复以及DNA和RNA合成的恢复。紫外线对DNA复制性合成的抑制作用略小于正常细胞。γ射线照射后，链断裂的重新连接正常，复制性DNA合成的动力学也正常。用硫酸二甲酯处理后，复制性DNA合成受到的影响与正常细胞类似，非预定DNA合成相对于正常细胞可能会增加，但46BR细胞中持续存在的链断裂比正常细胞更多。此外，46BR细胞对ADP-核糖基转移酶抑制剂3-氨基苯甲酰胺的毒性作用高度敏感。该酶参与烷基化损伤修复的连接步骤。本文提出了一个假说，认为46BR可能在DNA连接酶I方面存在缺陷。
