Evolution of alachlor-induced nasal neoplasms in the Long-Evans rat

The chloracetanilide herbicide alachlor (2-chloro-2',6-diethyl-N-(methoxyme thyl)-acetanilide) induces nasal neoplasms in rats following chronic dietar y exposure. The present study sought to identify the cellular origin and me chanisms of tumor induction and progression. Male Long-Evans rats were fed alachlor (0 or 126 mg/kg/day) beginning at 6 weeks of age. Following 1 mont h of alachlor ingestion, neither histological abnormalities nor enhanced ce ll division (assessed by BrdU incorporation) occurred in any region of the nasal cavity. Six months of alachlor exposure resulted in proliferation of basal and nonbasal cells in the olfactory mucosa while inducing nasal masse s in 7 of 15 animals. Tumors ranged from dysplastic plaques to polypoid ade nomas and originated in the olfactory regions of the nasal cavity. Neoplasm s were associated with regions of respiratory metaplasia and were often cov ered with a low cuboidal, poorly ciliated epithelium. Tumor cells did not e xpress characteristics of the olfactory mucosa, including olfactory marker protein (OMP, for neurons) and NMa (antibody recognizing cytochrome P450 [C YP] 2A3, found in Bowman's glands). Sites of plaque and tumor development c oincided with regions of NMa immunoreactivity. These data suggest that loca l metabolism is important in alachlor-induced olfactory tumors and support the concept that metaplastic respiratory epithelial cells give rise to the observed neoplasms.