Similarities in the formation and removal of covalent DNA adducts in benzo(a)pyrene-treated BALB/3T3 variant cells with different induced transformation frequencies.
Similarities in the formation and removal of covalent DNA adducts in benzo(a)pyrene-treated BALB/3T3 variant cells with different induced transformation frequencies.
复制标题
具有不同诱导转化频率的苯并(a)芘处理的 BALB/3T3 变异细胞中共价 DNA 加合物的形成和去除的相似性。
作者：
K. Lo;T. Kakunaga
从BALB/3 T3-A31克隆1中分离的细胞变体的类别显示对紫外光诱导的转化的高、中和低敏感性，也显示对苯并（a）芘（BP）诱导的转化的差异反应。另一方面，这些变异体对这些致癌物的杀伤作用表现出相同的易感性。BP结合DNA的程度被发现是非常相似的，在所有三类的变体转化条件下。通过高压液相色谱法分析来自变异细胞的BP：DNA加合物。在高度敏感、中度敏感和抗性变异体克隆中检测到相同的加合物（N2-（10 S-[7 R，8 S，9 R-三羟基-7，8，9，10-四氢苯并（a）芘]基）脱氧鸟苷和微量的7S对映体）。在所有三类变异细胞中，BP：DNA加合物的去除速率同样缓慢。这些结果表明，形成稳定的共价DNA加合物不是诱导转化的充分条件。因此，除了形成和去除稳定结合的BP：DNA共价加合物之外的过程是控制BALB/3 T3-A31克隆1变体细胞对BP诱导的转化的易感性的主要因素。
Classes of cell variants isolated from BALB/3T3-A31 clone 1 showing high, intermediate, and low susceptibility to ultraviolet light-induced transformation also demonstrated a differential response to benzo(a)pyrene (BP)-induced transformation. On the other hand, these variants showed an identical susceptibility to the killing effect of these carcinogens. The extent of BP binding to DNA was found to be very similar in all three classes of variants under transforming conditions. BP:DNA adducts from the variant cells were analyzed by high-pressure liquid chromatography. The same adducts (N2-(10S-[7R,8S,9R-trihydroxy-7,8,9,10-tetrahydrobenzo(a)pyrene]yl)deoxyguanosine and a minute amount of the 7S enantiomer) were detected in the highly susceptible, the intermediately susceptible, and the resistant variant clones. Removal of the BP:DNA adduct occurred at an equally slow rate in all three classes of variant cells. These results indicate that the formation of stable covalent DNA adducts is not a sufficient condition for induction of transformation. Processes other than formation and removal of the stably bound BP:DNA covalent adducts are thus major factors controlling the susceptibility of BALB/3T3-A31 clone 1 variant cells to BP-induced transformation.