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Strain-Specific Effects of Alachlor on Murine Olfactory Mucosal Responses

Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA, MaryBeth.Genter{at}UC.edu

Kathleen H. Goss

Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA

Joanna Groden

Department of Molecular Genetics, Biochemistry, and Microbiology and Howard Hughes Medical Institute, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA

Chloracetanilide herbicides are multisite carcinogens in rodents. Progression of alachlor-induced olfactory tumors in rats is accompanied by cytoplasmic accumulation and nuclear localization of β-catenin, suggesting activation of Wnt signaling. Female CD-1 mice were resistant to alachlor-induced olfactory carcinogenesis. The current studies were performed to determine whether ApcMin/+ mice, which have activated Wnt signaling due to mutation of the second allele of Apc, would be susceptible to alachlor olfactory carcinogenesis. Female and male ApcMin/+ mice, as well as Apc+/+ littermates received alachlor in the diet (260 mg/kg/d) for up to 3 months. Female A/J and C57BL/6J wild-type mice were also treated (for 10 and 14 months, respectively), as these strains vary in sensitivity to many respiratory tract insults. No olfactory mucosal tumors were observed in any of the mice, although alachlor-treated ApcMin/+ mice developed histological changes similar to those in alachlor-treated rats. Alachlor-treated A/J mice developed pronounced intracellular accumulation of amorphous eosinophilic material in the olfactory mucosa, foci of respiratory-like metaplasia, and hyperplasia of nasal mucus glands. A similar but less intense response was seen in C57BL/6J mice. Mice and rats had equivalent levels of the putative bioactivating enzyme (CYP2A) in olfactory mucosa, and mice had induced hepatic CYP3A and CYP2B enzymes with alachlor treatment, which may increase alachlor elimination. These studies extend previous observations by describing alachlor-induced olfactory mucosal changes in mice and suggest that hepatic metabolic enzyme induction may be responsible for resistance of mice to alachlor-induced olfactory carcinogenesis.

Key Words: Olfactory mucosa • alachlor • carcinogenesis • cross-species extrapolation • mouse model • Apc tumor suppressor.

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Toxicologic Pathology, Vol. 32, No. 6, 719-725 (2004)
DOI: 10.1080/01926230490885724


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This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Genter, M. B. Articles by Groden, J. Search for Related Content PubMed PubMed Citation Articles by Genter, M. B. Articles by Groden, J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ALACHLOR Social Bookmarking                         What's this?