Molecular analysis of styrene oxide-induced hprt mutation in human T-lymphocytes

Mutagenesis
T Bastlová, A Podlutsky

Abstract

Styrene-7,8-oxide (SO), the mutagenic in vivo metabolite of the widely used chemical monomer styrene, has been classified as a probable human carcinogen (IARC, 1994). We examined mutations in the hypoxanthine-guanine phosphoribosyl transferase (hprt) gene of primary human T-lymphocytes exposed to 0.2 mM SO for 6 days in vitro. PCR amplification and direct DNA sequencing were used to identify 55 SO-induced mutations from two experiments in which the mutation frequencies increased 3.6 and 4.8 times respectively, and 44 control mutations from untreated T-cell cultures. Base substitutions were the dominating type of mutation in both groups, with 35 and 23 independent changes, of which nine and six respectively, have not previously been described in human T-cells. Frameshift mutations (+/-1 bp) and small deletions (2-200 bp) were less frequent and splicing mutations more frequent among the SO-induced than among the control mutations. In SO-treated mutants, base substitutions in the coding region occurred at 15 sites, nine of which were AT bp, and in the splice donor and acceptor regions six of 10 mutated sites were AT bp. Altogether six independent mutations were found at site 539 in cells from the two SO experiments (four GC > AT a...Continue Reading

Citations

Jan 1, 1996·Environmental and Molecular Mutagenesis·A PodlutskyB Lambert
May 10, 2005·Mutation Research·Leigh M Henderson, Günter Speit
Jan 4, 2001·Chemico-biological Interactions·M Koskinen, K Plná
Aug 2, 2003·Cancer Detection and Prevention·P VodickaK Hemminki
Apr 5, 2005·Journal of Toxicology and Environmental Health. Part B, Critical Reviews·E R NestmannF Ratpan
Aug 23, 2001·Journal of Occupational and Environmental Medicine·M KoskinenK Hemminki
Jan 5, 2002·Environmental and Molecular Mutagenesis·M KanuriR S Lloyd
Dec 6, 2006·Drug Metabolism Reviews·Pavel VodickaFranz Oesch
Feb 13, 2001·Regulatory Toxicology and Pharmacology : RTP·K HemminkiC Zhao
Jun 23, 2000·Chemico-biological Interactions·M KoskinenK Hemminki

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