In Vivo Dosimetry off 4-Aminobiphenyl in Rats via a Cysteine Adduct in Hemoglobin

Laura C. Green; Paul L. Skipper; Robert J. Turesky; Matthew S. Bryant; Steven R. Tannenbaum

In Vivo Dosimetry off 4-Aminobiphenyl in Rats via a Cysteine Adduct in Hemoglobin

Laura C. Green, Paul L. Skipper, Robert J. Turesky, Matthew S. Bryant, Steven R. Tannenbaum

Medicinal Chemistry

Research output: Contribution to journal › Article › peer-review

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Abstract

The feasibility of monitoring doses of 4-aminobiphenyl (ABP) via adduction to hemoglobin was investigated. Rats dosed with ABP (from 0.5 μ gkg to 5 mg/kg) formed a stable covalent hemoglobin:ABP adduct. Approximately 5% of a single dose was bound as hemogtobin:ABP; chronic closing led to an accumulation of the adduct to a level 30 times greater than that found after a single dose. Facile in vitro hydrolysis of the adduct regenerated ABP, allowing detection at the sub-ng level. Human hemoglobin was also readily adducted, using N-hydroxy-ABP in vitro. The predominant site of adduction appeared to be the cysteine residue in hemoglobin. The use of such adducts as dosimeters for arylamine exposures in humans is discussed.

Original language	English (US)
Pages (from-to)	4254-4259
Number of pages	6
Journal	Cancer Research
Volume	44
Issue number	10
State	Published - Oct 1 1984

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title = "In Vivo Dosimetry off 4-Aminobiphenyl in Rats via a Cysteine Adduct in Hemoglobin",

abstract = "The feasibility of monitoring doses of 4-aminobiphenyl (ABP) via adduction to hemoglobin was investigated. Rats dosed with ABP (from 0.5 μ gkg to 5 mg/kg) formed a stable covalent hemoglobin:ABP adduct. Approximately 5% of a single dose was bound as hemogtobin:ABP; chronic closing led to an accumulation of the adduct to a level 30 times greater than that found after a single dose. Facile in vitro hydrolysis of the adduct regenerated ABP, allowing detection at the sub-ng level. Human hemoglobin was also readily adducted, using N-hydroxy-ABP in vitro. The predominant site of adduction appeared to be the cysteine residue in hemoglobin. The use of such adducts as dosimeters for arylamine exposures in humans is discussed.",

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T1 - In Vivo Dosimetry off 4-Aminobiphenyl in Rats via a Cysteine Adduct in Hemoglobin

AU - Green, Laura C.

AU - Skipper, Paul L.

AU - Turesky, Robert J.

AU - Bryant, Matthew S.

AU - Tannenbaum, Steven R.

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N2 - The feasibility of monitoring doses of 4-aminobiphenyl (ABP) via adduction to hemoglobin was investigated. Rats dosed with ABP (from 0.5 μ gkg to 5 mg/kg) formed a stable covalent hemoglobin:ABP adduct. Approximately 5% of a single dose was bound as hemogtobin:ABP; chronic closing led to an accumulation of the adduct to a level 30 times greater than that found after a single dose. Facile in vitro hydrolysis of the adduct regenerated ABP, allowing detection at the sub-ng level. Human hemoglobin was also readily adducted, using N-hydroxy-ABP in vitro. The predominant site of adduction appeared to be the cysteine residue in hemoglobin. The use of such adducts as dosimeters for arylamine exposures in humans is discussed.

AB - The feasibility of monitoring doses of 4-aminobiphenyl (ABP) via adduction to hemoglobin was investigated. Rats dosed with ABP (from 0.5 μ gkg to 5 mg/kg) formed a stable covalent hemoglobin:ABP adduct. Approximately 5% of a single dose was bound as hemogtobin:ABP; chronic closing led to an accumulation of the adduct to a level 30 times greater than that found after a single dose. Facile in vitro hydrolysis of the adduct regenerated ABP, allowing detection at the sub-ng level. Human hemoglobin was also readily adducted, using N-hydroxy-ABP in vitro. The predominant site of adduction appeared to be the cysteine residue in hemoglobin. The use of such adducts as dosimeters for arylamine exposures in humans is discussed.

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In Vivo Dosimetry off 4-Aminobiphenyl in Rats via a Cysteine Adduct in Hemoglobin

Abstract

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