Molecular Dosimetry of Endogenous and Exogenous O(6)-Methyl-dG and N7-Methyl-G Adducts Following Low Dose [D(3)]-Methylnitrosourea Exposures in Cultured Human Cells

[Image: see text] For DNA-reactive chemicals, a low dose linear assessment of cancer risk is the science policy default. In the present study, we quantitated the endogenous and exogenous N7-methyl-G and O(6)-methyl-dG adducts in human lymphoblastoid cells exposed to low dose [D(3)]-methylnitrosourea...

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Autores principales: Sharma, Vyom, Collins, Leonard B., Clement, Jean M., Zhang, Zhenfa, Nakamura, Jun, Swenberg, James A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998766/
https://www.ncbi.nlm.nih.gov/pubmed/24628573
http://dx.doi.org/10.1021/tx5000602
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author Sharma, Vyom
Collins, Leonard B.
Clement, Jean M.
Zhang, Zhenfa
Nakamura, Jun
Swenberg, James A.
author_facet Sharma, Vyom
Collins, Leonard B.
Clement, Jean M.
Zhang, Zhenfa
Nakamura, Jun
Swenberg, James A.
author_sort Sharma, Vyom
collection PubMed
description [Image: see text] For DNA-reactive chemicals, a low dose linear assessment of cancer risk is the science policy default. In the present study, we quantitated the endogenous and exogenous N7-methyl-G and O(6)-methyl-dG adducts in human lymphoblastoid cells exposed to low dose [D(3)]-methylnitrosourea. Endogenous amounts of both adducts remained nearly constant, while the exogenous adducts showed linear dose-responses. The data show that O(6)-methyl-dG adducts ≥1.8/10(8) dG correlated with published studies that demonstrated significant increases of mutations under these conditions. The combined results do not support linear extrapolations to zero when data are available for science-based regulations.
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spelling pubmed-39987662015-03-14 Molecular Dosimetry of Endogenous and Exogenous O(6)-Methyl-dG and N7-Methyl-G Adducts Following Low Dose [D(3)]-Methylnitrosourea Exposures in Cultured Human Cells Sharma, Vyom Collins, Leonard B. Clement, Jean M. Zhang, Zhenfa Nakamura, Jun Swenberg, James A. Chem Res Toxicol [Image: see text] For DNA-reactive chemicals, a low dose linear assessment of cancer risk is the science policy default. In the present study, we quantitated the endogenous and exogenous N7-methyl-G and O(6)-methyl-dG adducts in human lymphoblastoid cells exposed to low dose [D(3)]-methylnitrosourea. Endogenous amounts of both adducts remained nearly constant, while the exogenous adducts showed linear dose-responses. The data show that O(6)-methyl-dG adducts ≥1.8/10(8) dG correlated with published studies that demonstrated significant increases of mutations under these conditions. The combined results do not support linear extrapolations to zero when data are available for science-based regulations. American Chemical Society 2014-03-14 2014-04-21 /pmc/articles/PMC3998766/ /pubmed/24628573 http://dx.doi.org/10.1021/tx5000602 Text en Copyright © 2014 American Chemical Society
spellingShingle Sharma, Vyom
Collins, Leonard B.
Clement, Jean M.
Zhang, Zhenfa
Nakamura, Jun
Swenberg, James A.
Molecular Dosimetry of Endogenous and Exogenous O(6)-Methyl-dG and N7-Methyl-G Adducts Following Low Dose [D(3)]-Methylnitrosourea Exposures in Cultured Human Cells
title Molecular Dosimetry of Endogenous and Exogenous O(6)-Methyl-dG and N7-Methyl-G Adducts Following Low Dose [D(3)]-Methylnitrosourea Exposures in Cultured Human Cells
title_full Molecular Dosimetry of Endogenous and Exogenous O(6)-Methyl-dG and N7-Methyl-G Adducts Following Low Dose [D(3)]-Methylnitrosourea Exposures in Cultured Human Cells
title_fullStr Molecular Dosimetry of Endogenous and Exogenous O(6)-Methyl-dG and N7-Methyl-G Adducts Following Low Dose [D(3)]-Methylnitrosourea Exposures in Cultured Human Cells
title_full_unstemmed Molecular Dosimetry of Endogenous and Exogenous O(6)-Methyl-dG and N7-Methyl-G Adducts Following Low Dose [D(3)]-Methylnitrosourea Exposures in Cultured Human Cells
title_short Molecular Dosimetry of Endogenous and Exogenous O(6)-Methyl-dG and N7-Methyl-G Adducts Following Low Dose [D(3)]-Methylnitrosourea Exposures in Cultured Human Cells
title_sort molecular dosimetry of endogenous and exogenous o(6)-methyl-dg and n7-methyl-g adducts following low dose [d(3)]-methylnitrosourea exposures in cultured human cells
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998766/
https://www.ncbi.nlm.nih.gov/pubmed/24628573
http://dx.doi.org/10.1021/tx5000602
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