Mutational spectrum of chromium(VI) in human cells.
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.
Chen
J
J
Department of Civil and Environmental Engineering, Whitaker College of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge 02139.
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D001483:Base Sequence; D002478:Cells, Cultured; D002857:Chromium / Q000633:toxicity*; D017931:DNA Primers; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008969:Molecular Sequence Data; D009153:Mutagens / Q000633:toxicity*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D013866:Thioguanine / Q000633:toxicity
D017931:DNA Primers; D009153:Mutagens; D002857:Chromium; D007041:Hypoxanthine Phosphoribosyltransferase; D013866:Thioguanine