Tissue distribution and macromolecular binding of extremely low doses of [14C]-benzene in B6C3F1 mice

Moire Robertson Creek, Chitra Mani, John S. Vogel, Ken W Turteltaub

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

The tissue distribution and macromolecular binding of benzene was studied over a dose range spanning nine-orders of magnitude to determine the nature of the dose-response and to establish benzene's internal dosimetry at doses encompassing human environmental exposures. [14C]-Benzene was administered to B6C3F1 male mice at doses ranging between 700 pg/kg and 500 mgkg body wt. Tissues, DNA and protein were analyzed for [14C]-benzene content between 0 and 48 h post-exposure (625 Ng/kg and 5 μg/kg dose) by accelerator mass spectrometry (AMS). [14C]-Benzene levels were highest in the liver and peaked within 0.5 h of exposure. Liver DNA adduct levels peaked at 0.5 h, in contrast to bone marrow DNA adduct levels, which peaked at 12-24 h. Dose-response assessments at 1 h showed that adducts and tissue available doses increased linearly with administered dose up to doses of 16 mg/kg body wt. Tissue available doses and liver protein adducts plateau above the 16 mg/kg dose. Furthermore, a larger percentage of the available dose in bone marrow bound to DNA relative to liver. Protein adduct levels were 9- to 43-fold greater than DNA adduct levels. These data show that benzene is bioavailable at human-relevant doses and that DNA and protein adduct formation is linear with dose over a dose range spanning eight orders of magnitude. Finally, these data show that the dose of bioactive metabolites is greater to the bone marrow than the liver and suggests that protein adducts may contribute to benzene's hematoxicity.

Original languageEnglish (US)
Pages (from-to)2421-2427
Number of pages7
JournalCarcinogenesis
Volume18
Issue number12
DOIs
StatePublished - Dec 1997

Fingerprint

Tissue Distribution
Benzene
DNA Adducts
Liver
Bone Marrow
Proteins
DNA
Environmental Exposure
Mass Spectrometry

ASJC Scopus subject areas

  • Cancer Research

Cite this

Tissue distribution and macromolecular binding of extremely low doses of [14C]-benzene in B6C3F1 mice. / Creek, Moire Robertson; Mani, Chitra; Vogel, John S.; Turteltaub, Ken W.

In: Carcinogenesis, Vol. 18, No. 12, 12.1997, p. 2421-2427.

Research output: Contribution to journalArticle

Creek, Moire Robertson ; Mani, Chitra ; Vogel, John S. ; Turteltaub, Ken W. / Tissue distribution and macromolecular binding of extremely low doses of [14C]-benzene in B6C3F1 mice. In: Carcinogenesis. 1997 ; Vol. 18, No. 12. pp. 2421-2427.
@article{a59cf6b0acce40cdbb08a5e06eeb9ca7,
title = "Tissue distribution and macromolecular binding of extremely low doses of [14C]-benzene in B6C3F1 mice",
abstract = "The tissue distribution and macromolecular binding of benzene was studied over a dose range spanning nine-orders of magnitude to determine the nature of the dose-response and to establish benzene's internal dosimetry at doses encompassing human environmental exposures. [14C]-Benzene was administered to B6C3F1 male mice at doses ranging between 700 pg/kg and 500 mgkg body wt. Tissues, DNA and protein were analyzed for [14C]-benzene content between 0 and 48 h post-exposure (625 Ng/kg and 5 μg/kg dose) by accelerator mass spectrometry (AMS). [14C]-Benzene levels were highest in the liver and peaked within 0.5 h of exposure. Liver DNA adduct levels peaked at 0.5 h, in contrast to bone marrow DNA adduct levels, which peaked at 12-24 h. Dose-response assessments at 1 h showed that adducts and tissue available doses increased linearly with administered dose up to doses of 16 mg/kg body wt. Tissue available doses and liver protein adducts plateau above the 16 mg/kg dose. Furthermore, a larger percentage of the available dose in bone marrow bound to DNA relative to liver. Protein adduct levels were 9- to 43-fold greater than DNA adduct levels. These data show that benzene is bioavailable at human-relevant doses and that DNA and protein adduct formation is linear with dose over a dose range spanning eight orders of magnitude. Finally, these data show that the dose of bioactive metabolites is greater to the bone marrow than the liver and suggests that protein adducts may contribute to benzene's hematoxicity.",
author = "Creek, {Moire Robertson} and Chitra Mani and Vogel, {John S.} and Turteltaub, {Ken W}",
year = "1997",
month = "12",
doi = "10.1093/carcin/18.12.2421",
language = "English (US)",
volume = "18",
pages = "2421--2427",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",
number = "12",

}

TY - JOUR

T1 - Tissue distribution and macromolecular binding of extremely low doses of [14C]-benzene in B6C3F1 mice

AU - Creek, Moire Robertson

AU - Mani, Chitra

AU - Vogel, John S.

AU - Turteltaub, Ken W

PY - 1997/12

Y1 - 1997/12

N2 - The tissue distribution and macromolecular binding of benzene was studied over a dose range spanning nine-orders of magnitude to determine the nature of the dose-response and to establish benzene's internal dosimetry at doses encompassing human environmental exposures. [14C]-Benzene was administered to B6C3F1 male mice at doses ranging between 700 pg/kg and 500 mgkg body wt. Tissues, DNA and protein were analyzed for [14C]-benzene content between 0 and 48 h post-exposure (625 Ng/kg and 5 μg/kg dose) by accelerator mass spectrometry (AMS). [14C]-Benzene levels were highest in the liver and peaked within 0.5 h of exposure. Liver DNA adduct levels peaked at 0.5 h, in contrast to bone marrow DNA adduct levels, which peaked at 12-24 h. Dose-response assessments at 1 h showed that adducts and tissue available doses increased linearly with administered dose up to doses of 16 mg/kg body wt. Tissue available doses and liver protein adducts plateau above the 16 mg/kg dose. Furthermore, a larger percentage of the available dose in bone marrow bound to DNA relative to liver. Protein adduct levels were 9- to 43-fold greater than DNA adduct levels. These data show that benzene is bioavailable at human-relevant doses and that DNA and protein adduct formation is linear with dose over a dose range spanning eight orders of magnitude. Finally, these data show that the dose of bioactive metabolites is greater to the bone marrow than the liver and suggests that protein adducts may contribute to benzene's hematoxicity.

AB - The tissue distribution and macromolecular binding of benzene was studied over a dose range spanning nine-orders of magnitude to determine the nature of the dose-response and to establish benzene's internal dosimetry at doses encompassing human environmental exposures. [14C]-Benzene was administered to B6C3F1 male mice at doses ranging between 700 pg/kg and 500 mgkg body wt. Tissues, DNA and protein were analyzed for [14C]-benzene content between 0 and 48 h post-exposure (625 Ng/kg and 5 μg/kg dose) by accelerator mass spectrometry (AMS). [14C]-Benzene levels were highest in the liver and peaked within 0.5 h of exposure. Liver DNA adduct levels peaked at 0.5 h, in contrast to bone marrow DNA adduct levels, which peaked at 12-24 h. Dose-response assessments at 1 h showed that adducts and tissue available doses increased linearly with administered dose up to doses of 16 mg/kg body wt. Tissue available doses and liver protein adducts plateau above the 16 mg/kg dose. Furthermore, a larger percentage of the available dose in bone marrow bound to DNA relative to liver. Protein adduct levels were 9- to 43-fold greater than DNA adduct levels. These data show that benzene is bioavailable at human-relevant doses and that DNA and protein adduct formation is linear with dose over a dose range spanning eight orders of magnitude. Finally, these data show that the dose of bioactive metabolites is greater to the bone marrow than the liver and suggests that protein adducts may contribute to benzene's hematoxicity.

UR - http://www.scopus.com/inward/record.url?scp=0031428098&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031428098&partnerID=8YFLogxK

U2 - 10.1093/carcin/18.12.2421

DO - 10.1093/carcin/18.12.2421

M3 - Article

C2 - 9450490

AN - SCOPUS:0031428098

VL - 18

SP - 2421

EP - 2427

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - 12

ER -