Strain-specific of alachlor on murine olfactory mucosal responses.
Chloracetanilide herbicides are multisite carcinogens in rodents. Progression of alachlor-induced olfactory tumors in rats is accompanied by cytoplasmic accumulation and nuclear localization of beta-catenin, suggesting activation of Wint signaling. Female CD-1 mice were resistant to alachlor-induced olfactory carcinogenesis. The current studies were performed to determine whether Apc(Min/+) 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 Apc(Min/+) 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 Apc(Min/+) 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.
Genter
Mary Beth
MB
Department of Environmental Health, ML 670056, 3223 Eden Ave., 144 Kettering, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA. MaryBeth.Genter@UC.edu
Goss
Kathleen H
KH
Groden
Joanna
J
D000081:Acetamides / Q000633:toxicity*; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000032:analysis; D065637:Cytochrome P-450 CYP2A6; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D006899:Mixed Function Oxygenases / Q000032:analysis; D009831:Olfactory Mucosa / Q000187:drug effects* / Q000473:pathology; D013045:Species Specificity
D000081:Acetamides; C000188:alachlor; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; D065637:Cytochrome P-450 CYP2A6