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
Mar 10, 2001·Mutation Research·M MognatoL Celotti
Sep 6, 2001·Mutation Research·P VodickaK Hemminki
Aug 2, 2003·Cancer Detection and Prevention·P VodickaK Hemminki
Aug 18, 2000·Mutation Research·S Díaz-LleraB Lambert
Nov 27, 1999·Mutation Research·P VodickaK Hemminki
Jun 29, 2002·Mutation Research·Pavel VodickaKari Hemminki
Apr 5, 2005·Journal of Toxicology and Environmental Health. Part B, Critical Reviews·E R NestmannF Ratpan
Nov 8, 2001·Carcinogenesis·P Noori, S M Hou
Feb 22, 2007·Mutagenesis·Lode GodderisH Veulemans
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
Mar 16, 2021·NAR Cancer·Xiaoju HuSubhajyoti De
Feb 13, 2001·Regulatory Toxicology and Pharmacology : RTP·K HemminkiC Zhao
Jun 23, 2000·Chemico-biological Interactions·M KoskinenK Hemminki
May 29, 2000·Organic Letters·M Koskinen, K Hemminki