在CHO细胞中，特定烷基化碱基与由乙基亚硝基脲和硫酸二乙酯诱导的两个基因位点突变之间的关系。

Relationship between specific alkylated bases and mutations at two gene loci induced by ethylnitrosourea and diethyl sulfate in CHO cells.

作者信息

Bignami M, Vitelli A, Di Muccio A, Terlizzese M, Calcagnile A, Zapponi G A, Lohman P H, den Engelse L, Dogliotti E

机构信息

Laboratory of Applied Toxicology, Istituto Superiore di Sanità, Rome, Italy.

出版信息

Mutat Res. 1988 Jan;193(1):43-51. doi: 10.1016/0167-8817(88)90006-5.

DOI:10.1016/0167-8817(88)90006-5

PMID:2827012

Abstract

DNA adduct formation and induction of mutations at 2 gene loci, hypoxanthine-guanine-phosphoribosyltransferase (HPRT) and Na,K-ATPase, were determined simultaneously in Chinese hamster ovary (CHO) cells after treatment with 2 ethylating agents, ethylnitrosourea (ENU) or diethyl sulfate (DES). Doses of DES and ENU, which resulted in equal levels of O6-ethylguanine (O6-EtGua) and O4-ethylthymine (O4-EtThy) in the DNA, were found to induce very similar frequencies of 6-thioguanine-resistant (6-TGr) mutants. Formation of these DNA adducts might therefore be correlated with mutations induced at the HPRT locus. When, however, the same analysis was applied to ouabain-resistant (ouar) mutants, it was found that, at similar levels of O6-EtGua and O4-EtThy, DES induced many more ouar mutants than ENU. This result supports the notion that primary DNA lesions other than O6-EtGua and O4-EtThy are involved in the fixation of ENU- and DES-induced mutations at the Na,K-ATPase gene locus.

摘要

在用两种乙基化试剂，即乙基亚硝基脲（ENU）或硫酸二乙酯（DES）处理中国仓鼠卵巢（CHO）细胞后，同时测定了2个基因位点，即次黄嘌呤 - 鸟嘌呤磷酸核糖转移酶（HPRT）和钠钾ATP酶处的DNA加合物形成及突变诱导情况。发现导致DNA中O6 - 乙基鸟嘌呤（O6 - EtGua）和O4 - 乙基胸腺嘧啶（O4 - EtThy）水平相等的DES和ENU剂量，诱导出的6 - 硫鸟嘌呤抗性（6 - TGr）突变体频率非常相似。因此，这些DNA加合物的形成可能与HPRT位点诱导的突变相关。然而，当对哇巴因抗性（ouar）突变体进行相同分析时发现，在O6 - EtGua和O4 - EtThy水平相似的情况下，DES诱导出的ouar突变体比ENU多得多。这一结果支持了这样一种观点，即在钠钾ATP酶基因位点上，除O6 - EtGua和O4 - EtThy之外的原发性DNA损伤参与了ENU和DES诱导的突变的固定。