人类细胞中六价铬的突变谱。

Mutational spectrum of chromium(VI) in human cells.

作者信息

Chen J, Thilly W G

机构信息

Department of Civil and Environmental Engineering, Whitaker College of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge 02139.

出版信息

Mutat Res. 1994 Jan-Feb;323(1-2):21-7. doi: 10.1016/0165-7992(94)90040-x.

DOI:10.1016/0165-7992(94)90040-x

PMID:7508562

Abstract

The mutational spectrum of K2Cr2O7 on the low melting domain within exon 3 of hypoxanthine guanine phosphoribosyl transferase (hprt) gene was obtained from 6-thioguanine-resistant (6TGr) human lymphoblasts (TK6). Using a combination of high-fidelity polymerase chain reaction (PCR) and denaturing gradient gel electrophoresis (DGGE), we found four chromium(VI) induced hotspots in a 104-bp target sequence. The hotspots were C:G-->A:T at bp 243, representing 4.5% of 6TGr mutants; A:T-->T:A at bp 247 (2.0%); G:C-->A:T at bp 289 (2.5%) and C:G-->T:A at bp 312 (4.0%). Mutational hotspots at bp 243 have previously been determined for hydrogen peroxide (C:G-->G:C) and benzo[a]pyrene diol epoxide (C:G-->A:T). Two of the hotspots, bp 243 and 289, arose in a common quadruplet 5'-ACAT-3' in the untranscribed and transcribed strands respectively.

摘要

次黄嘌呤鸟嘌呤磷酸核糖转移酶（hprt）基因第3外显子低熔点结构域上K2Cr2O7的突变谱来自对6-硫鸟嘌呤抗性（6TGr）人淋巴母细胞（TK6）的研究。通过结合高保真聚合酶链反应（PCR）和变性梯度凝胶电泳（DGGE），我们在一个104bp的目标序列中发现了四个铬（VI）诱导的热点。这些热点分别是：第243位碱基处的C:G→A:T，占6TGr突变体的4.5%；第247位碱基处的A:T→T:A（2.0%）；第289位碱基处的G:C→A:T（2.5%）；以及第312位碱基处的C:G→T:A（4.0%）。之前已确定第243位碱基处的突变热点在过氧化氢作用下为（C:G→G:C），在苯并[a]芘二醇环氧化物作用下为（C:G→A:T）。其中两个热点，即第243位和第289位碱基，分别出现在非转录链和转录链中的一个共同四联体5'-ACAT-3'中。