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Title: Quantitative predictability of carcinogenicity of the covalent binding index of chemicals to DNA: Comparison of the in vivo and in vitro assays

Abstract

The capability of covalent binding to DNA to predict the initiating potential of chemical carcinogens was compared for the assays performed in vivo (rodent liver DNA) and in vitro (purified DNA incubated in the presence of mouse and rat liver microsomes). A quantitative correlation between DNA adducts and carcinogenic potency was investigated. The in vivo assay appeared slightly, but not significantly, more predictive than the in vitro assay. Also predictivity was slightly higher both in vivo and in vitro when we referred to liver carcinogenicity instead of overall carcinogenicity. The predictive ability found for DNA covalent binding (both in vivo and in vitro) was similar to that of many short-term tests (such as mutagenicity, DNA damage/repair, SCEs, and cell transformation tests). The covalent DNA binding, measured after incubation with DNA in vitro in the presence of liver microsomes, could therefore be a reasonable short-term test offering greater rapidity of execution and requiring the sacrifice of fewer animals than the corresponding in vivo test.

Authors:
; ; ;  [1];  [2]
  1. (Universita di Genova/Istituto Nazionale per la Ricerca sul Cancro (Italy))
  2. (Universita di Bologna (Italy))
Publication Date:
OSTI Identifier:
5447591
Resource Type:
Journal Article
Journal Name:
Environmental Health Perspectives; (United States)
Additional Journal Information:
Journal Volume: 84; Journal ID: ISSN 0091-6765
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; CARCINOGENESIS; BIOASSAY; CARCINOGENS; DNA ADDUCTS; AFLATOXINS; BENZENE; BENZOPYRENE; CELL TRANSFORMATIONS; CHLORINATED AROMATIC HYDROCARBONS; DNA REPAIR; EMS; IN VITRO; IN VIVO; INDOLES; LIVER; MICE; MICROSOMES; MOLECULAR BIOLOGY; MUTAGENESIS; NITROSO COMPOUNDS; POLYCYCLIC AROMATIC HYDROCARBONS; RATS; SISTER CHROMATID EXCHANGES; ADDUCTS; ANIMALS; ANTIGENS; AROMATICS; AZAARENES; AZOLES; BIOLOGICAL RECOVERY; BIOLOGICAL REPAIR; BODY; CELL CONSTITUENTS; CHROMOSOMAL ABERRATIONS; CONDENSED AROMATICS; DIGESTIVE SYSTEM; ESTERS; GLANDS; HALOGENATED AROMATIC HYDROCARBONS; HETEROCYCLIC COMPOUNDS; HYDROCARBONS; MAMMALS; MATERIALS; MUTAGENS; MUTATIONS; ORGANIC CHLORINE COMPOUNDS; ORGANIC COMPOUNDS; ORGANIC HALOGEN COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; ORGANIC SULFUR COMPOUNDS; ORGANS; PATHOGENESIS; PYRROLES; RECOVERY; REPAIR; RIBOSOMES; RODENTS; SULFONIC ACID ESTERS; TOXIC MATERIALS; TOXINS; VERTEBRATES; 560300* - Chemicals Metabolism & Toxicology

Citation Formats

Taningher, M., Saccomanno, G., Santi, L., Parodi, S., and Grilli, S. Quantitative predictability of carcinogenicity of the covalent binding index of chemicals to DNA: Comparison of the in vivo and in vitro assays. United States: N. p., 1990. Web. doi:10.1289/ehp.9084183.
Taningher, M., Saccomanno, G., Santi, L., Parodi, S., & Grilli, S. Quantitative predictability of carcinogenicity of the covalent binding index of chemicals to DNA: Comparison of the in vivo and in vitro assays. United States. doi:10.1289/ehp.9084183.
Taningher, M., Saccomanno, G., Santi, L., Parodi, S., and Grilli, S. Thu . "Quantitative predictability of carcinogenicity of the covalent binding index of chemicals to DNA: Comparison of the in vivo and in vitro assays". United States. doi:10.1289/ehp.9084183.
@article{osti_5447591,
title = {Quantitative predictability of carcinogenicity of the covalent binding index of chemicals to DNA: Comparison of the in vivo and in vitro assays},
author = {Taningher, M. and Saccomanno, G. and Santi, L. and Parodi, S. and Grilli, S.},
abstractNote = {The capability of covalent binding to DNA to predict the initiating potential of chemical carcinogens was compared for the assays performed in vivo (rodent liver DNA) and in vitro (purified DNA incubated in the presence of mouse and rat liver microsomes). A quantitative correlation between DNA adducts and carcinogenic potency was investigated. The in vivo assay appeared slightly, but not significantly, more predictive than the in vitro assay. Also predictivity was slightly higher both in vivo and in vitro when we referred to liver carcinogenicity instead of overall carcinogenicity. The predictive ability found for DNA covalent binding (both in vivo and in vitro) was similar to that of many short-term tests (such as mutagenicity, DNA damage/repair, SCEs, and cell transformation tests). The covalent DNA binding, measured after incubation with DNA in vitro in the presence of liver microsomes, could therefore be a reasonable short-term test offering greater rapidity of execution and requiring the sacrifice of fewer animals than the corresponding in vivo test.},
doi = {10.1289/ehp.9084183},
journal = {Environmental Health Perspectives; (United States)},
issn = {0091-6765},
number = ,
volume = 84,
place = {United States},
year = {1990},
month = {3}
}