A recombinant model for assessing the role of GSTM1 in styrene-7,8-oxide toxicity and mutagenicity

Alison J. Shield, Barbara J S Sanderson

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Styrene-7,8-oxide (SO) is a highly reactive epoxide able to undergo reactions with endogenous nucleophiles, such as DNA. SO is inactivated by glutathione-S-transferase M1 (GSTM1). This detoxification enzyme is absent in approximately one-half of Caucasian (49%) populations. A GSTM1 recombinant human lymphoblastoid cell line (FB7) was generated from a GSTM1 negative parental cell line (WIL2NS). GSTM1 status was determined using RT-PCR and immunochemistry. Cells were challenged with a range of SO doses and subsequent toxicity (population growth in flasks) and genotoxicity (mutations at the HPRT locus) were monitored. FB7 (GSTM1 positive) exhibited greater cell survival after SO exposure relative to the GSTM1 negative parental line. The IC50 following a 1 h exposure to SO was 0.5 mM for WIL2NS, compared to greater than 2.5 mM for FB7. The extrapolated IC50 for FB7 was 5.5 mM. Significantly fewer mutant cells were induced by SO for FB7 than for WIL2NS at equivalent doses of SO. These findings suggest that the sensitivity of cells to styrene-7,8-oxide is influenced by GSTM1 status and that a recombinant GSTM1 positive cell line can efficiently detoxify styrene-7,8-oxide.

Original languageEnglish
Pages (from-to)61-68
Number of pages8
JournalToxicology
Volume195
Issue number1
DOIs
Publication statusPublished - 15 Jan 2004
Externally publishedYes

Fingerprint

styrene oxide
Toxicity
Cells
Cell Line
Inhibitory Concentration 50
Immunochemistry
Hypoxanthine Phosphoribosyltransferase
glutathione S-transferase M1
Detoxification
Nucleophiles
Population Growth
Epoxy Compounds

Cite this

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abstract = "Styrene-7,8-oxide (SO) is a highly reactive epoxide able to undergo reactions with endogenous nucleophiles, such as DNA. SO is inactivated by glutathione-S-transferase M1 (GSTM1). This detoxification enzyme is absent in approximately one-half of Caucasian (49{\%}) populations. A GSTM1 recombinant human lymphoblastoid cell line (FB7) was generated from a GSTM1 negative parental cell line (WIL2NS). GSTM1 status was determined using RT-PCR and immunochemistry. Cells were challenged with a range of SO doses and subsequent toxicity (population growth in flasks) and genotoxicity (mutations at the HPRT locus) were monitored. FB7 (GSTM1 positive) exhibited greater cell survival after SO exposure relative to the GSTM1 negative parental line. The IC50 following a 1 h exposure to SO was 0.5 mM for WIL2NS, compared to greater than 2.5 mM for FB7. The extrapolated IC50 for FB7 was 5.5 mM. Significantly fewer mutant cells were induced by SO for FB7 than for WIL2NS at equivalent doses of SO. These findings suggest that the sensitivity of cells to styrene-7,8-oxide is influenced by GSTM1 status and that a recombinant GSTM1 positive cell line can efficiently detoxify styrene-7,8-oxide.",
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A recombinant model for assessing the role of GSTM1 in styrene-7,8-oxide toxicity and mutagenicity. / Shield, Alison J.; Sanderson, Barbara J S.

In: Toxicology, Vol. 195, No. 1, 15.01.2004, p. 61-68.

Research output: Contribution to journalArticle

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AB - Styrene-7,8-oxide (SO) is a highly reactive epoxide able to undergo reactions with endogenous nucleophiles, such as DNA. SO is inactivated by glutathione-S-transferase M1 (GSTM1). This detoxification enzyme is absent in approximately one-half of Caucasian (49%) populations. A GSTM1 recombinant human lymphoblastoid cell line (FB7) was generated from a GSTM1 negative parental cell line (WIL2NS). GSTM1 status was determined using RT-PCR and immunochemistry. Cells were challenged with a range of SO doses and subsequent toxicity (population growth in flasks) and genotoxicity (mutations at the HPRT locus) were monitored. FB7 (GSTM1 positive) exhibited greater cell survival after SO exposure relative to the GSTM1 negative parental line. The IC50 following a 1 h exposure to SO was 0.5 mM for WIL2NS, compared to greater than 2.5 mM for FB7. The extrapolated IC50 for FB7 was 5.5 mM. Significantly fewer mutant cells were induced by SO for FB7 than for WIL2NS at equivalent doses of SO. These findings suggest that the sensitivity of cells to styrene-7,8-oxide is influenced by GSTM1 status and that a recombinant GSTM1 positive cell line can efficiently detoxify styrene-7,8-oxide.

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