Impact of structural and metabolic variations on the toxicity and carcinogenicity of hydroxy- and alkoxy-substituted allyl- and propenylbenzenes

I. M C M Rietjens, Samuel Monroe Cohen, S. Fukushima, N. J. Gooderham, S. Hecht, L. J. Marnett, R. L. Smith, T. B. Adams, M. Bastaki, C. G. Harman, S. V. Taylor

Research output: Contribution to journalReview article

21 Citations (Scopus)

Abstract

The metabolic fate of a compound is determined by numerous factors including its chemical structure. Although the metabolic options for a variety of functional groups are well understood and can often provide a rationale for the comparison of toxicity based on structural analogy, at times quite minor structural variations may have major consequences for metabolic outcomes and toxicity. In this perspective, the effects of structural variations on metabolic outcomes is detailed for a group of related hydroxy- and alkoxy-substituted allyl- and propenylbenzenes. These classes of compounds are naturally occurring constituents of a variety of botanical-based food items. The classes vary from one another by the presence or absence of alkylation of their para-hydroxyl substituents and/or the position of the double bond in the alkyl side chain. We provide an overview of how these subtle structural variations alter the metabolism of these important food-borne compounds, ultimately influencing their toxicity, particularly their DNA reactivity and carcinogenic potential. The data reveal that detailed knowledge of the consequences of subtle structural variations for metabolism is essential for adequate comparison of structurally related chemicals. Taken together, it is concluded that predictions in toxicological risk assessment should not be performed on the basis of structural analogy only but should include an analogy of metabolic pathways across compounds and species.

Original languageEnglish (US)
Pages (from-to)1092-1103
Number of pages12
JournalChemical Research in Toxicology
Volume27
Issue number7
DOIs
StatePublished - Jul 21 2014

Fingerprint

Toxicity
Metabolism
Food
Alkylation
Metabolic Networks and Pathways
Hydroxyl Radical
Toxicology
Risk assessment
Functional groups
DNA
alkoxyl radical

ASJC Scopus subject areas

  • Toxicology

Cite this

Impact of structural and metabolic variations on the toxicity and carcinogenicity of hydroxy- and alkoxy-substituted allyl- and propenylbenzenes. / Rietjens, I. M C M; Cohen, Samuel Monroe; Fukushima, S.; Gooderham, N. J.; Hecht, S.; Marnett, L. J.; Smith, R. L.; Adams, T. B.; Bastaki, M.; Harman, C. G.; Taylor, S. V.

In: Chemical Research in Toxicology, Vol. 27, No. 7, 21.07.2014, p. 1092-1103.

Research output: Contribution to journalReview article

Rietjens, IMCM, Cohen, SM, Fukushima, S, Gooderham, NJ, Hecht, S, Marnett, LJ, Smith, RL, Adams, TB, Bastaki, M, Harman, CG & Taylor, SV 2014, 'Impact of structural and metabolic variations on the toxicity and carcinogenicity of hydroxy- and alkoxy-substituted allyl- and propenylbenzenes', Chemical Research in Toxicology, vol. 27, no. 7, pp. 1092-1103. https://doi.org/10.1021/tx500109s
Rietjens, I. M C M ; Cohen, Samuel Monroe ; Fukushima, S. ; Gooderham, N. J. ; Hecht, S. ; Marnett, L. J. ; Smith, R. L. ; Adams, T. B. ; Bastaki, M. ; Harman, C. G. ; Taylor, S. V. / Impact of structural and metabolic variations on the toxicity and carcinogenicity of hydroxy- and alkoxy-substituted allyl- and propenylbenzenes. In: Chemical Research in Toxicology. 2014 ; Vol. 27, No. 7. pp. 1092-1103.
@article{cb4483bfa2eb4e9cbf91b0a034be0ac7,
title = "Impact of structural and metabolic variations on the toxicity and carcinogenicity of hydroxy- and alkoxy-substituted allyl- and propenylbenzenes",
abstract = "The metabolic fate of a compound is determined by numerous factors including its chemical structure. Although the metabolic options for a variety of functional groups are well understood and can often provide a rationale for the comparison of toxicity based on structural analogy, at times quite minor structural variations may have major consequences for metabolic outcomes and toxicity. In this perspective, the effects of structural variations on metabolic outcomes is detailed for a group of related hydroxy- and alkoxy-substituted allyl- and propenylbenzenes. These classes of compounds are naturally occurring constituents of a variety of botanical-based food items. The classes vary from one another by the presence or absence of alkylation of their para-hydroxyl substituents and/or the position of the double bond in the alkyl side chain. We provide an overview of how these subtle structural variations alter the metabolism of these important food-borne compounds, ultimately influencing their toxicity, particularly their DNA reactivity and carcinogenic potential. The data reveal that detailed knowledge of the consequences of subtle structural variations for metabolism is essential for adequate comparison of structurally related chemicals. Taken together, it is concluded that predictions in toxicological risk assessment should not be performed on the basis of structural analogy only but should include an analogy of metabolic pathways across compounds and species.",
author = "Rietjens, {I. M C M} and Cohen, {Samuel Monroe} and S. Fukushima and Gooderham, {N. J.} and S. Hecht and Marnett, {L. J.} and Smith, {R. L.} and Adams, {T. B.} and M. Bastaki and Harman, {C. G.} and Taylor, {S. V.}",
year = "2014",
month = "7",
day = "21",
doi = "10.1021/tx500109s",
language = "English (US)",
volume = "27",
pages = "1092--1103",
journal = "Chemical Research in Toxicology",
issn = "0893-228X",
publisher = "American Chemical Society",
number = "7",

}

TY - JOUR

T1 - Impact of structural and metabolic variations on the toxicity and carcinogenicity of hydroxy- and alkoxy-substituted allyl- and propenylbenzenes

AU - Rietjens, I. M C M

AU - Cohen, Samuel Monroe

AU - Fukushima, S.

AU - Gooderham, N. J.

AU - Hecht, S.

AU - Marnett, L. J.

AU - Smith, R. L.

AU - Adams, T. B.

AU - Bastaki, M.

AU - Harman, C. G.

AU - Taylor, S. V.

PY - 2014/7/21

Y1 - 2014/7/21

N2 - The metabolic fate of a compound is determined by numerous factors including its chemical structure. Although the metabolic options for a variety of functional groups are well understood and can often provide a rationale for the comparison of toxicity based on structural analogy, at times quite minor structural variations may have major consequences for metabolic outcomes and toxicity. In this perspective, the effects of structural variations on metabolic outcomes is detailed for a group of related hydroxy- and alkoxy-substituted allyl- and propenylbenzenes. These classes of compounds are naturally occurring constituents of a variety of botanical-based food items. The classes vary from one another by the presence or absence of alkylation of their para-hydroxyl substituents and/or the position of the double bond in the alkyl side chain. We provide an overview of how these subtle structural variations alter the metabolism of these important food-borne compounds, ultimately influencing their toxicity, particularly their DNA reactivity and carcinogenic potential. The data reveal that detailed knowledge of the consequences of subtle structural variations for metabolism is essential for adequate comparison of structurally related chemicals. Taken together, it is concluded that predictions in toxicological risk assessment should not be performed on the basis of structural analogy only but should include an analogy of metabolic pathways across compounds and species.

AB - The metabolic fate of a compound is determined by numerous factors including its chemical structure. Although the metabolic options for a variety of functional groups are well understood and can often provide a rationale for the comparison of toxicity based on structural analogy, at times quite minor structural variations may have major consequences for metabolic outcomes and toxicity. In this perspective, the effects of structural variations on metabolic outcomes is detailed for a group of related hydroxy- and alkoxy-substituted allyl- and propenylbenzenes. These classes of compounds are naturally occurring constituents of a variety of botanical-based food items. The classes vary from one another by the presence or absence of alkylation of their para-hydroxyl substituents and/or the position of the double bond in the alkyl side chain. We provide an overview of how these subtle structural variations alter the metabolism of these important food-borne compounds, ultimately influencing their toxicity, particularly their DNA reactivity and carcinogenic potential. The data reveal that detailed knowledge of the consequences of subtle structural variations for metabolism is essential for adequate comparison of structurally related chemicals. Taken together, it is concluded that predictions in toxicological risk assessment should not be performed on the basis of structural analogy only but should include an analogy of metabolic pathways across compounds and species.

UR - http://www.scopus.com/inward/record.url?scp=84904641005&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84904641005&partnerID=8YFLogxK

U2 - 10.1021/tx500109s

DO - 10.1021/tx500109s

M3 - Review article

C2 - 24857813

AN - SCOPUS:84904641005

VL - 27

SP - 1092

EP - 1103

JO - Chemical Research in Toxicology

JF - Chemical Research in Toxicology

SN - 0893-228X

IS - 7

ER -