Dose-response relationship in complete oral 4NQO-carcinogenesis in rats

Groups of 48 Wistar rats were subjected to thrice-weekly palatal application of the carcinogen 4-nitro-quinoline 1-oxide (4NQO) in propylene glycol 18, 12, 6 or 2 times, each 255 nmol 4NQO, in order to examine the relationship between the dose of the carcinogen and the tumour response. Other groups were treated with solvent alone or were left untreated. When the carcinogen was applied 18 or 12 times, squamous cell or verrucous carcinomas developed in 50% of the rats in 11 and 12 months, respectively, whereas rats subjected to the carcinogen 6 times demonstrated a 50% cancer rate in 23 months. Rats twice exposed to the carcinogen demonstrated a tumour rate of 25% in 30 months. Decreasing doses of 4NQO thus prolonged the latency period and decreased the tumour rate. The tumour development in the animals subjected to two carcinogen applications was significantly different from the tumour development among the solvent-treated animals, indicating that application of 255 nmol may approximate the initiating dose of 4NQO to be used in a two- or multi-stage carcinogenesis protocol. Most of the carcinomas, either squamous cell or verrucous, were located to the hard palate and to the gingival region of the upper jaw. Impaction of hair, bedding material and food was thought to promote the carcinogenic process.