Antioxidant perturbations in the olfactory mucosa of alachlor-treated rats.

The chloracetanilide herbicide alachlor (2-chloro-2',6'-diethyl-N-(methoxymethyl)acetanilide) induces olfactory mucosal tumors in rats following chronic dietary exposure. Previous reports demonstrated that alachlor exposure was associated with depletion of glutathione (GSH) in liver in vivo and in vitro, but did not address this issue in the target tissue for the carcinogenic response. In this study we investigated a potential oxidative stress pathway in olfactory tissue by examining perturbations in olfactory mucosal antioxidants.

Progression of alachlor-induced olfactory mucosal tumours.

Alachlor is an herbicide used primarily in the production of corn (maize), peanuts, and soybeans and is associated with cancer of the nasal cavity, thyroid, and stomach in rats. Previous work from our laboratory demonstrated that the nasal cavity tumours originate from the olfactory mucosa, and that neoplasms were present following 6 months of exposure (126 mg/kg/day in the diet). The studies presented herein were conducted to determine more precisely the earliest time point at which alachlor-induced tumours were present, and to describe the histological changes that occur en route to tumour formation.

Genomic analysis of alachlor-induced oncogenesis in rat olfactory mucosa.

Alachlor induces olfactory mucosal tumors in rats in a highly ordered temporal process. We used GeneChip analysis to test the hypothesis that histological progression and oncogenic transformation are accompanied by gene expression changes that might yield clues as to the molecular pathogenesis of tumor formation. Acute alachlor exposure caused upregulation of matrix metalloproteinases (MMP)-2 and -9, tissue inhibitor of metalloproteinase-1, carboxypeptidase Z, and other genes related to extracellular matrix homeostasis.