Bignami M, Vitelli A, Di Muccio A, Terlizzese M, Calcagnile A, Zapponi G A, Lohman P H, den Engelse L, Dogliotti E
Laboratory of Applied Toxicology, Istituto Superiore di Sanità, Rome, Italy.
Mutat Res. 1988 Jan;193(1):43-51. doi: 10.1016/0167-8817(88)90006-5.
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.
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。
