Mutagenicity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) when activated by hamster pancreatic duct epithelial cells: A chemopreventive role for glutathione

Terence Lawson, Carol Kolar, Tanya Reyes

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

We have shown a role for glutathione (GSH) in the detoxification of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) using mutagenicity in V79 cells as the end-point. Immortalized hamster pancreas duct epithelial cells (CK cells) were used to metabolize PhIP in this assay. Intracellular GSH concentrations were lowered by treatment with buthionine sulfoximine (BSO) and were raised by treatment with sodium sulfite. BSO treatment (10 mM, 4 h) reduced the GSH concentration in V79 cells from 18 ± 1 to 6 ± 1 nmol/mg protein, 4 h after treatment. The mutation frequency of PhIP in these V79 cells rose from 15 ± 2 to 34 ± 4 mutants/106 survivors in BSO-treated V79 cells. In a related experiment both CK and V79 cells were treated with sulfite. Sulfite treatment (2 mM, 4 h) produced a greater reduction in PhIP mutagenicity when the V79 cells were treated with sulfite (from 15 ± 2 to 3 ± 1 mutants/106 survivors) than when the CK cells were treated (from 15 ± 2 to 7 ± 2 mutants/106 survivors). These data show a relationship between intracellular GSH concentration and the mutagenicity of PhIP.

Original languageEnglish (US)
Pages (from-to)73-78
Number of pages6
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume375
Issue number1
DOIs
StatePublished - Apr 14 1997

Fingerprint

Pancreatic Ducts
Cricetinae
Glutathione
Epithelial Cells
Buthionine Sulfoximine
Sulfites
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine
Mutation Rate
Pancreas

Keywords

  • Glutathione
  • Heterocyclic amine
  • Mutagenicity
  • Pancreas duct epithelium
  • V79 cell

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Health, Toxicology and Mutagenesis

Cite this

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title = "Mutagenicity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) when activated by hamster pancreatic duct epithelial cells: A chemopreventive role for glutathione",
abstract = "We have shown a role for glutathione (GSH) in the detoxification of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) using mutagenicity in V79 cells as the end-point. Immortalized hamster pancreas duct epithelial cells (CK cells) were used to metabolize PhIP in this assay. Intracellular GSH concentrations were lowered by treatment with buthionine sulfoximine (BSO) and were raised by treatment with sodium sulfite. BSO treatment (10 mM, 4 h) reduced the GSH concentration in V79 cells from 18 ± 1 to 6 ± 1 nmol/mg protein, 4 h after treatment. The mutation frequency of PhIP in these V79 cells rose from 15 ± 2 to 34 ± 4 mutants/106 survivors in BSO-treated V79 cells. In a related experiment both CK and V79 cells were treated with sulfite. Sulfite treatment (2 mM, 4 h) produced a greater reduction in PhIP mutagenicity when the V79 cells were treated with sulfite (from 15 ± 2 to 3 ± 1 mutants/106 survivors) than when the CK cells were treated (from 15 ± 2 to 7 ± 2 mutants/106 survivors). These data show a relationship between intracellular GSH concentration and the mutagenicity of PhIP.",
keywords = "Glutathione, Heterocyclic amine, Mutagenicity, Pancreas duct epithelium, V79 cell",
author = "Terence Lawson and Carol Kolar and Tanya Reyes",
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T1 - Mutagenicity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) when activated by hamster pancreatic duct epithelial cells

T2 - A chemopreventive role for glutathione

AU - Lawson, Terence

AU - Kolar, Carol

AU - Reyes, Tanya

PY - 1997/4/14

Y1 - 1997/4/14

N2 - We have shown a role for glutathione (GSH) in the detoxification of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) using mutagenicity in V79 cells as the end-point. Immortalized hamster pancreas duct epithelial cells (CK cells) were used to metabolize PhIP in this assay. Intracellular GSH concentrations were lowered by treatment with buthionine sulfoximine (BSO) and were raised by treatment with sodium sulfite. BSO treatment (10 mM, 4 h) reduced the GSH concentration in V79 cells from 18 ± 1 to 6 ± 1 nmol/mg protein, 4 h after treatment. The mutation frequency of PhIP in these V79 cells rose from 15 ± 2 to 34 ± 4 mutants/106 survivors in BSO-treated V79 cells. In a related experiment both CK and V79 cells were treated with sulfite. Sulfite treatment (2 mM, 4 h) produced a greater reduction in PhIP mutagenicity when the V79 cells were treated with sulfite (from 15 ± 2 to 3 ± 1 mutants/106 survivors) than when the CK cells were treated (from 15 ± 2 to 7 ± 2 mutants/106 survivors). These data show a relationship between intracellular GSH concentration and the mutagenicity of PhIP.

AB - We have shown a role for glutathione (GSH) in the detoxification of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) using mutagenicity in V79 cells as the end-point. Immortalized hamster pancreas duct epithelial cells (CK cells) were used to metabolize PhIP in this assay. Intracellular GSH concentrations were lowered by treatment with buthionine sulfoximine (BSO) and were raised by treatment with sodium sulfite. BSO treatment (10 mM, 4 h) reduced the GSH concentration in V79 cells from 18 ± 1 to 6 ± 1 nmol/mg protein, 4 h after treatment. The mutation frequency of PhIP in these V79 cells rose from 15 ± 2 to 34 ± 4 mutants/106 survivors in BSO-treated V79 cells. In a related experiment both CK and V79 cells were treated with sulfite. Sulfite treatment (2 mM, 4 h) produced a greater reduction in PhIP mutagenicity when the V79 cells were treated with sulfite (from 15 ± 2 to 3 ± 1 mutants/106 survivors) than when the CK cells were treated (from 15 ± 2 to 7 ± 2 mutants/106 survivors). These data show a relationship between intracellular GSH concentration and the mutagenicity of PhIP.

KW - Glutathione

KW - Heterocyclic amine

KW - Mutagenicity

KW - Pancreas duct epithelium

KW - V79 cell

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