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

Mutation Research/DNA Repair Reports Pub Date : 1988-01-01 DOI:10.1016/0167-8817(88)90006-5

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

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引用次数: 16

Abstract

DNA adduct formation and induction of mutations at gene loci, hypoxanthine-guanine-phosphoribosyltranferase (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 O⁶-ethylthymine (O⁴-EtThy) in the DNA, were found to induce very similar frequencies of 6-thioguanine-resistant (6-TG^r) 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 (our^r) mutants, it was found that, at similar levels of O⁶-EtGua and O⁴-EtThy, DES induced many more oua^r 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.

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乙基亚硝基脲和硫酸二乙酯诱导CHO细胞特异性烷基化碱基与两个基因位点突变的关系

用2种乙基亚硝基脲(ENU)和硫酸二乙酯(DES)处理中国地鼠卵巢(CHO)细胞，同时测定DNA加合物的形成和对次黄嘌呤-鸟嘌呤-磷酸核糖基转移酶(HPRT)和Na - k - atp酶基因位点突变的诱导。DES和ENU剂量导致DNA中相同水平的o6 -乙基鸟嘌呤(O6-EtGua)和o6 -乙基胸腺嘧啶(o4 - eththy)，发现诱导6-硫鸟嘌呤抗性(6-TGr)突变体的频率非常相似。因此，这些DNA加合物的形成可能与HPRT位点诱导的突变有关。然而，当同样的分析应用于抗硫脲(ourr)突变体时，发现在相同水平的O6-EtGua和O4-EtThy下，DES诱导的our突变体比ENU多得多。这一结果支持了一种观点，即除了O6-EtGua和O4-EtThy外，其他DNA损伤也参与了ENU和des诱导的Na, k - atp酶基因位点突变的固定。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Mutation Research/DNA Repair Reports

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