4NQO carcinogenesis: A mouse model of oral cavity squamous cell carcinoma

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Abstract
Background. A murine model of oral cavity carcinogenesis is needed to study the molecular aspects of malignant transformation. 4-Nitroquinoline-1-oxide (4NQO), a water-soluble carcinogen, produces squamous cell carcinoma in rodents. Protocols were designed to investigate the temporal aspects of neoplastic transformation. Methods. 4NQO was applied topically to mouse palates for up to 16 weeks. Mice were observed and killed from 24 to 49 weeks. Results. A spectrum of lesions ranging from atypia to moderately differentiated invasive squamous cell carcinoma (SCC) was produced. The severity of the lesions corresponded to the duration of treatment and the length of observation. There was no gross or microscopic evidence of an inflammatory reaction to 4NQO. The lesions were focal and normal mucosa predominated in the treated mice. Conclusion. 4NQO reliably produced preneoplastic and malignant oral cavity lesions, which morphologically and histologically mimic human head and neck cancer. Lesions develop long after 4NQO exposure and without an inflammatory response. Thus, the model should be useful for molecular analysis of neoplastic transformation. © 1994 John Wiley & Sons, Inc.