Pardini C, Piras A, Voliani M, Rainaldi G, Mariani L, Taverna P, D'Incalci M, Citti L
Genetica e Biochemica Tossicologica dell'Istituto di Mutagenesi e Differenziamento-CNR, Pisa, Italy.
Mutat Res. 1992 Oct;283(2):125-9. doi: 10.1016/0165-7992(92)90144-7.
In mammalian cells, under aerobic conditions, ionizing radiations and radiomimetic chemical agents can induce an enzymatic activity involved in DNA repair, O6-alkylguanine-DNA alkyltransferase (O6-AT). This catalytic protein is active against alkyl-radical-induced DNA damages. This induction was proposed to be linked to the formation of hydroxyl radicals. The possible involvement of O6-AT in the defense mechanism of the cell against aerobic radiation damage was investigated by comparing the X-ray sensitivity of two Chinese hamster ovary (CHO) cell lines, the first deficient (CHO mex-) and the second proficient by transfection of O6-AT (CHO mex+). The colony-forming ability after X-irradiation was appreciably reduced in CHO mex- in comparison to CHO mex+ cells. Nevertheless, pretreatment of proficient cells with O6-methylguanine, a specific inhibitor of O6-AT, reduced the DNA repair activity but did not modify the degree of sensitivity to X-rays of the CHO mex+ cells. Since the glutathione concentrations as well as the DNA damage amounts induced by X-irradiation were comparable in the variously treated cell lines, these results suggest that the observed induction of O6-AT by ionizing radiation in aerobic conditions could be a generalized rather than a specific response to damage by radicals.
在哺乳动物细胞中，在有氧条件下，电离辐射和拟辐射化学试剂可诱导参与DNA修复的一种酶活性，即O6-烷基鸟嘌呤-DNA烷基转移酶（O6-AT）。这种催化蛋白对烷基自由基诱导的DNA损伤具有活性。有人提出这种诱导与羟基自由基的形成有关。通过比较两种中国仓鼠卵巢（CHO）细胞系的X射线敏感性，研究了O6-AT在细胞抵抗有氧辐射损伤防御机制中的可能作用，第一种细胞系缺陷（CHO mex-），第二种细胞系通过转染O6-AT而具有该酶活性（CHO mex+）。与CHO mex+细胞相比，CHO mex-细胞在X射线照射后的集落形成能力明显降低。然而，用O6-甲基鸟嘌呤（O6-AT的特异性抑制剂）预处理具有该酶活性的细胞，可降低DNA修复活性，但并未改变CHO mex+细胞对X射线的敏感程度。由于在各种处理的细胞系中，谷胱甘肽浓度以及X射线照射诱导的DNA损伤量相当，这些结果表明，在有氧条件下电离辐射诱导的O6-AT可能是一种普遍反应，而非对自由基损伤的特异性反应。
