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Title: Covalent binding of (/sup 14/C)-2,6-dimethylaniline to DNA of rat liver and ethmoid turbinate

Abstract

The xylidide 2,6-dimethylaniline (2,6-DMA) has produced carcinomas and papillary adenomas in the nasal cavity of rats at high dietary doses (3000 ppm) in a 2-yr bioassay. The objective of the present study was to measure the covalent binding of 2,6-DMA to DNA of rat ethmoid turbinate tissues and, for comparison, to DNA of rat liver. The potent hepatocarcinogen 2-acetylaminofluorene (AAF) was studied as a positive control for adduct formation and covalent binding index (CBI) calculation. Both 2,6-DMA and AAF were administered as /sup 14/C-(ring)-labeled agents to naive rats and to rats pretreated for 9 d with unlabeled 2,6-DMA or AAF. The CBI value for 2,6-DMA adduct formation with ethmoid turbinate DNA was below the assay's sensitivity limit in nonpretreated rats, but increased to 41.9 in rats pretreated with unlabeled 2,6-DMA. It also increased from 0.6 in nonpretreated to 7.9 in liver of pretreated rats. The opposite pattern, however, was observed for AAF. In nonpretreated rats considerable adduct formation was observed in liver (CBI = 271.5) and modest values (CBI = 39.3) were calculated for ethmoid turbinate tissues. Pretreatment with unlabeled AAF caused a significant decrease in CBI values, to 18.3 for liver and less than 0.5 for ethmoid turbinate. Themore » results suggest that there may be value in conducting DNA covalent binding assays in both naive animals and animals pretreated with the test article.« less

Authors:
; ;
Publication Date:
Research Org.:
Louisiana State Univ., Baton Rouge (USA)
OSTI Identifier:
5713903
Resource Type:
Journal Article
Journal Name:
J. Toxicol. Environ. Health; (United States)
Additional Journal Information:
Journal Volume: 27:1
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; 59 BASIC BIOLOGICAL SCIENCES; ANILINE; BIOCHEMICAL REACTION KINETICS; DNA; BIOASSAY; DNA ADDUCTS; BIOSYNTHESIS; FLUORENE; TOXICITY; ADENOMAS; CARBON 14 COMPOUNDS; CARCINOGENESIS; CARCINOMAS; COMPARATIVE EVALUATIONS; EPITHELIUM; LIVER; NOSE; RATS; TRACER TECHNIQUES; ADDUCTS; AMINES; ANIMAL TISSUES; ANIMALS; AROMATICS; BODY; BODY AREAS; CONDENSED AROMATICS; DIGESTIVE SYSTEM; DISEASES; FACE; GLANDS; HEAD; HYDROCARBONS; ISOTOPE APPLICATIONS; KINETICS; LABELLED COMPOUNDS; MAMMALS; NEOPLASMS; NUCLEIC ACIDS; ORGANIC COMPOUNDS; ORGANS; PATHOGENESIS; REACTION KINETICS; RESPIRATORY SYSTEM; RODENTS; SYNTHESIS; TISSUES; VERTEBRATES; 560300* - Chemicals Metabolism & Toxicology; 550201 - Biochemistry- Tracer Techniques

Citation Formats

Short, C.R., Joseph, M., and Hardy, M.L. Covalent binding of (/sup 14/C)-2,6-dimethylaniline to DNA of rat liver and ethmoid turbinate. United States: N. p., 1989. Web. doi:10.1080/15287398909531280.
Short, C.R., Joseph, M., & Hardy, M.L. Covalent binding of (/sup 14/C)-2,6-dimethylaniline to DNA of rat liver and ethmoid turbinate. United States. doi:10.1080/15287398909531280.
Short, C.R., Joseph, M., and Hardy, M.L. Sun . "Covalent binding of (/sup 14/C)-2,6-dimethylaniline to DNA of rat liver and ethmoid turbinate". United States. doi:10.1080/15287398909531280.
@article{osti_5713903,
title = {Covalent binding of (/sup 14/C)-2,6-dimethylaniline to DNA of rat liver and ethmoid turbinate},
author = {Short, C.R. and Joseph, M. and Hardy, M.L.},
abstractNote = {The xylidide 2,6-dimethylaniline (2,6-DMA) has produced carcinomas and papillary adenomas in the nasal cavity of rats at high dietary doses (3000 ppm) in a 2-yr bioassay. The objective of the present study was to measure the covalent binding of 2,6-DMA to DNA of rat ethmoid turbinate tissues and, for comparison, to DNA of rat liver. The potent hepatocarcinogen 2-acetylaminofluorene (AAF) was studied as a positive control for adduct formation and covalent binding index (CBI) calculation. Both 2,6-DMA and AAF were administered as /sup 14/C-(ring)-labeled agents to naive rats and to rats pretreated for 9 d with unlabeled 2,6-DMA or AAF. The CBI value for 2,6-DMA adduct formation with ethmoid turbinate DNA was below the assay's sensitivity limit in nonpretreated rats, but increased to 41.9 in rats pretreated with unlabeled 2,6-DMA. It also increased from 0.6 in nonpretreated to 7.9 in liver of pretreated rats. The opposite pattern, however, was observed for AAF. In nonpretreated rats considerable adduct formation was observed in liver (CBI = 271.5) and modest values (CBI = 39.3) were calculated for ethmoid turbinate tissues. Pretreatment with unlabeled AAF caused a significant decrease in CBI values, to 18.3 for liver and less than 0.5 for ethmoid turbinate. The results suggest that there may be value in conducting DNA covalent binding assays in both naive animals and animals pretreated with the test article.},
doi = {10.1080/15287398909531280},
journal = {J. Toxicol. Environ. Health; (United States)},
number = ,
volume = 27:1,
place = {United States},
year = {1989},
month = {1}
}