STUDY OF THE OXYGEN EFFECT IN RADIATION BIOLOGY

有证据表明，氧效应（氧使细胞对 电离辐射）是由基因决定的，因此，必须有 在效果上有缺陷的突变体。 建议分离和研究这种 突变体，以便在分子水平上了解 氧气的影响。 已经发现的证据表明， 辐射后修复过程，至少对于直接辐射效应。 它 已经证明，伽马射线在没有氧气的情况下， 不存在时，形成DNA、谷胱甘肽（GSH）和 其他细胞物质，并建议切除这些 加合物照射后是更高的细胞存活的机制， 没有氧气。 本文提出：（1）研究在体标记 DNA与GSH及其它物质在甲苯化或EDTA-Tris处理的E. 大肠杆菌和尿素处理的噬菌体T4颗粒（II颗粒，其DNA是不稳定的 （2）使用具有通过照射产生的加合物的T1 DNA， 分离E.大肠杆菌辐射后修复缺陷突变体。 非突变体 会通过修复T1 DNA而自杀，缺陷突变体会 在幸存者中得到了丰富，并因他们无法成为 通过缺氧来防止辐射。 最终，两个 突变体细胞蛋白质的三维电泳凝胶 将与非突变体的蛋白质进行比较，以鉴定蛋白质 随后可以在体外研究其对DNA的作用 加合物 氧气的作用在医学上是重要的，因为大多数肿瘤细胞都处于 降低氧张力，因此具有抗辐射性。 理解 分子水平上的影响可以导致方法的发展， 减少辐射阻力。 本研究涉及遗传学、生物化学、 生物物理学和分子生物学。

There is evidence that the oxygen effect (oxygen sensitizes cells to ionizing radiation) is genetically determined and, therefore, there must be mutants defective in the effect. It is proposed to isolate and study such mutants in order to understand at the molecular level the mechanism(s) of the oxygen effect. Evidence has been found that indicates the effect is a post-irradiation repair process, at least for direct radiation effects. It has been demonstrated that gamma-radiation in the absence of oxygen, but not in its presence, forms an adduct between DNA, glutathione (GSH), and other cellular substances, and it is proposed that excision of these adducts post-irradiation is the mechanism of higher cell survival in the absence of oxygen. It is proposed: (1) to study the in vivo labeling of DNA with GSH and other substances in toluenized or EDTA-Tris treated E. coli and urea-treated phage T4 particles (II particle) whose DNA is labile to DNAse; (2) to use T1 DNA which has adducts produced by irradiation to isolate E. coli mutants defective in post-irradiation repair. Nonmutants will commit suicide by repairing the T1 DNA and defective mutants will be enriched among the survivors and recognized by their inability to be protected from radiation by oxygen deprivation. Ultimately, two dimensional electrophoretic gels of the cellular proteins of the mutants will be compared with the proteins of nonmutants to identify the protein(s) involved which subsequently can be studied in vitro for its action on DNA adducts. The oxygen effect is important medically because most tumor cells are at reduced oxygen tension and therefore radiation resistant. Understanding the effect at the molecular level can lead to the development of methods to lessen radiation resistance. This study involves the methodologies of genetics, biochemistry, biophysics, and molecular biology.