Locus specificity in the mutability of L5178Y mouse lymphoma cells: the role of multilocus lesions.
Locus specificity in the mutability of L5178Y mouse lymphoma cells: the role of multilocus lesions.
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L5178Y 小鼠淋巴瘤细胞突变性的位点特异性：多位点病变的作用。
DOI：
10.1073/pnas.83.12.4379
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发表时间：
1986
影响因子：
11.1
通讯作者：
Hozier,J
中科院分区：
文献类型：
--
作者：
Evans,HH;Mencl,J;Horng,MF;Ricanati,M;Sanchez,C;Hozier,J
小鼠L5178Y品系LY-S及其亲本品系LY-R对各种诱变剂的细胞毒性作用的相对敏感性不同，即与品系LY-R相比，品系LY-S对单个诱变剂的敏感性更高、更不敏感或类似敏感。然而，经X射线、紫外线或烷化剂处理后，菌株LY-S在次黄嘌呤(鸟嘌呤)磷酸核糖转移酶(HPRT)基因座上的突变程度均低于菌株LY-R。在本工作中，我们分离了胸苷激酶(TK)基因(11号染色体)上杂合的菌株LY-R和LY-S的亚克隆。我们发现，LY-S TK+/TK-杂合菌株在X-射线、UV辐射或甲烷磺酸乙酯处理后，在TK基因座上表现出比杂合LY-R菌株更高或更高的突变性。经这些诱变剂处理后，除1株杂合子LY-R株只有一条11号染色体，且TK基因座对X辐射的诱变性较差外，所有杂合子菌株在TK基因座上的致突变性都远高于HPRT基因座。根据这些结果，我们认为，由于修复缺陷，经辐射或烷化剂处理后，LY-S菌株的DNA中会形成多位点损伤；当靶基因与必需基因紧密连锁并位于半合子染色体区域(例如，X染色体上的Hprt基因座或11号染色体单体的TK基因座)时，多位点损伤会导致存活突变株的恢复较差；而x-射线在修复有效和修复缺陷的半合染色体区域的基因座上，是一种相对较差的诱变剂。
Mouse L5178Y strain LY-S and its parental strain LY-R differ in their comparative sensitivities to the cytotoxic effects of various mutagenic agents--i.e., strain LY-S has been found to be more sensitive, less sensitive, or similarly sensitive to individual agents in comparison to strain LY-R. Nevertheless, strain LY-S has been found to be uniformly less mutable than strain LY-R at the hypoxanthine (guanine) phosphoribosyltransferase (Hprt) locus following treatment with x-radiation, UV radiation, or alkylating agents. In the present work we have isolated subclones of strains LY-R and LY-S that are heterozygous at the thymidine kinase (Tk) locus (chromosome 11). We have found that a heterozygous LY-S Tk+/Tk- strain shows as high or higher mutability at the Tk locus than do heterozygous LY-R strains following treatment with x-radiation, UV radiation, or ethyl methanesulfonate. Mutability of all heterozygous strains at the Tk locus is much higher than at the Hprt locus following treatment with these mutagenic agents, with the exception of one heterozygous LY-R strain that possesses only one chromosome 11 and that is poorly mutable at the Tk locus by x-radiation. On the basis of these results, we have suggested that because of a repair deficiency, multilocus lesions are formed in the DNA of LY-S strains following treatment with radiation or alkylating agents; multilocus lesions lead to poor recovery of viable mutants when the target locus is closely linked to essential genes and situated on a hemizygous chromosomal region (e.g., the Hprt locus on the X chromosome or the Tk locus in strains monosomic for chromosome 11); and x-radiation is a relatively poor mutagen at loci situated on hemizygous chromosomal regions, in repair-efficient and repair-deficient cells, because of its tendency to form multilocus lesions.