Bertsche U
Br J Cancer Suppl. 1984;6:121-7.
Cultures of Ehrlich ascites tumour cells (EATC) were treated before and after X-irradiation with the membrane active drugs chlorpromazine (CPZ) and procaine. Under hypoxic conditions of irradiation CPZ sensitized cells and was most effective at about 50 microM, whereas at higher drug concentrations the extent of sensitization was less. Sensitization was however not observed in cultures supplemented with vitamin E. Likewise, CPZ inhibited repair of potentially lethal damage (RPLD) measured by delayed plating of stationary cell cultures either using the colony forming ability or micronucleus formation as endpoints. Procaine, on the other hand, was found to sensitize cells only slightly under hypoxia and protected slightly under oxic conditions in the concentration range from 10-100 mM. Both drugs induced an increase in ATP content at these concentrations. Since it has also been observed that these drugs cause depletion of intracellular sulfhydryl groups which may serve for protection of membrane sites, it is assumed that the radiobiological effects observed arise mainly from an influence on cellular and nuclear membranes where lipid bilayer fluidity and conformational status of membrane-bound enzymes may be changed. The possible role of heterochromatin anchored or near to the nuclear membrane as a radiation sensitive compartment of the cell is discussed.
用膜活性药物氯丙嗪（CPZ）和普鲁卡因对艾氏腹水瘤细胞（EATC）培养物在X射线照射前后进行处理。在照射的缺氧条件下，CPZ使细胞致敏，在约50微摩尔时最有效，而在较高药物浓度下致敏程度较小。然而，在补充维生素E的培养物中未观察到致敏现象。同样，CPZ抑制通过以集落形成能力或微核形成作为终点对静止细胞培养物进行延迟接种来测量的潜在致死损伤（RPLD）的修复。另一方面，发现普鲁卡因在缺氧条件下仅使细胞轻微致敏，在10 - 100毫摩尔的浓度范围内在有氧条件下有轻微保护作用。在这些浓度下，两种药物均诱导ATP含量增加。由于还观察到这些药物会导致细胞内巯基的消耗，而巯基可能用于保护膜位点，因此推测观察到的放射生物学效应主要源于对细胞膜和核膜的影响，其中脂质双分子层流动性和膜结合酶的构象状态可能会发生变化。讨论了作为细胞辐射敏感区室的锚定在核膜上或靠近核膜的异染色质的可能作用。
