Tsuji H, Takahashi E, Tsuji S, Tobari I, Shiomi T, Sato K
Mutat Res. 1987 May;178(1):107-16. doi: 10.1016/0027-5107(87)90092-3.
To determine the mutual relationships between cell survival and induction of sister-chromatid exchanges (SCEs) as well as chromosomal aberrations (CAs), mutagen-induced SCEs and CAs were analyzed in an ionizing radiation-sensitive mutant (M10) and an alkylating agent-sensitive mutant (MS 1) isolated from mouse lymphoma L5178Y cells. The levels of CA induction in both mutants strictly corresponded to the sensitivity to lethal effects of mutagens, except that caffeine-induced CAs in M10 are considerably lower than those in L5178Y. The results clearly indicate that except for caffeine-induced CAs in M10, mutagen-induced lethal lesions are responsible for CA induction. In contrast, SCE induction in mutants was complicated. In M10, hypersensitive to killing by gamma-rays, methyl methanesulfonate (MMS), and 4-nitroquinoline 1-oxide (4NQO), but not sensitive to UV or caffeine, the frequency of SCEs induced by gamma-rays was barely higher than that in L5178Y, and the frequencies of MMS- and UV-induced SCEs were similar to those in L5178Y, but 4NQO- and caffeine-induced SCEs were markedly lower than those in L5178Y. MS 1, which is hypersensitive to MMS and caffeine, but not sensitive to UV or 4NQO, responded to caffeine with an enhanced frequency of SCEs and had a normal frequency of MMS-induced SCEs, but a reduced frequency of UV- and 4NQO-induced SCEs. Thus, susceptibility to SCE induction by mutagens is not necessarily correlated with sensitivity of mutants to cell killing and/or CA induction by mutagens. Furthermore, the spontaneous levels of SCEs are lower in M10 and higher in MS 1 than that in L5178Y (Tsuji et al., 1987). Based on these results, we speculate that M10 may be partially defective in the processes for the formation of SCEs caused by mutagens. On the other hand, MS 1 may modify SCE formation-related lesions induced by UV and 4NQO to some repair intermediates that do not cause SCE formation. In addition, MMS-induced lethal lesions in MS 1 may not be responsible for SCE induction whereas caffeine-induced lethal lesions are closely correlated with SCE induction. Thus, the lesions or mechanisms involved in SCE production are in part different from those responsible for cell lethality or CA production.
为了确定细胞存活与姐妹染色单体交换（SCEs）以及染色体畸变（CAs）诱导之间的相互关系，我们对从小鼠淋巴瘤L5178Y细胞中分离出的电离辐射敏感突变体（M10）和烷化剂敏感突变体（MS 1）中诱变剂诱导的SCEs和CAs进行了分析。除了咖啡因诱导M10中的CAs明显低于L5178Y中的CAs外，两个突变体中CA的诱导水平与诱变剂致死效应的敏感性严格对应。结果清楚地表明，除了咖啡因诱导M10中的CAs外，诱变剂诱导的致死性损伤是CA诱导的原因。相比之下，突变体中SCE的诱导情况较为复杂。M10对γ射线、甲基磺酸甲酯（MMS）和4-硝基喹啉1-氧化物（4NQO）杀伤敏感，但对紫外线或咖啡因不敏感，γ射线诱导的SCE频率仅略高于L5178Y，MMS和紫外线诱导SCEs的频率与L5178Y相似，但4NQO和咖啡因诱导的SCEs明显低于L5178Y。MS 1对MMS和咖啡因敏感，但对紫外线或4NQO不敏感，对咖啡因的反应是SCEs频率增加，MMS诱导的SCE频率正常，但紫外线和4NQO诱导的SCE频率降低。因此，诱变剂诱导SCE的易感性不一定与突变体对诱变剂细胞杀伤和/或CA诱导的敏感性相关。此外，M10中SCE的自发水平低于L5178Y，而MS 1中则高于L5178Y（Tsuji等人，1987）。基于这些结果，我们推测M10在由诱变剂引起的SCE形成过程中可能存在部分缺陷。另一方面，MS 1可能将紫外线和4NQO诱导的与SCE形成相关损伤修饰为一些不会导致SCE形成的修复中间体。此外，MS 1中MMS诱导的致死性损伤可能不是SCE诱导的原因，而咖啡因诱导的致死性损伤与SCE诱导密切相关。因此，参与SCE产生的损伤或机制部分不同于导致细胞致死或CA产生的损伤或机制。
