INDUCTION BY 4-NITROQUINOLINE-1-OXIDE OF ORAL EPITHELIAL DYSPLASIA AND NEOPLASIA IN SCURVY-PRONE OSTEOGENIC DISORDER SHIONOGI (ODS) RATS

Carcinogenesis by 4-nitroquinoline-1-oxine (NQO) in the oral mucosa is a reliable method of obtaining oral mucosal squamous cell carcinoma ( OMSCC) and allows examination of various stages of oral cancer develop ment. In vivo and in vitro studies have indicated that L-ascorbic acid (AA) may have a role in cancer prevention. The Wistar ''scurvy-prone' ' osteogenic disorder Shionogi (ODS) rat of the od/od substrain is una ble to synthesize AA and requires supplementation for its survival. Th is study examined the effects of NeO on the oral mucosa of ODS and out bred Wistar rats. NeO (0.5%) was applied topically to the palatal muco sa of 72 male ODS and 36 outbred Wistar rats three times weekly for 4, 8, 12, 16, 20, and 24 wks. The ODS rats were divided so that 36 rats were given 2.5 g/l AA in the drinking water and 36 rats were given 0.3 3 g/l AA. Vehicle-treated and untreated control animals were included. The rats were killed two weeks after the final NeO application, and t he tissues were examined. Epithelial dysplasia was assessed using a mo dified Smith and Pindborg (1969) index. The ordered categorical scores were analyzed appropriately. Plasma AA levels were checked in ODS and outbred rats at the start and end of the experiment. The results indi cated that the oral mucosa of the ODS and outbred rats were susceptibl e to NQO but that the rate of dysplasia and OMSCC development differed between them, with more rapid changes being found in the ODS rats (p less than or equal to 0.05). No significant difference was found in th e dysplasia scores and in the rate of OMSCC development between ODS ra ts given 2.5 g/l of AA and ODS rats given 0.33 g/l of AA (p less than or equal to 0.05). No epithelial changes were observed in the palatal mucosa of vehicle-treated and untreated controls. The plasma AA level mean (+/- SEM) was 56 +/- 6 mu M for the outbred rats, 8 +/- 1 mu M fo r the ODS rats given 0.33 g/l AA supplementation, and 29 +/- 2 mu M fo r the ODS rats given 2.5 g/l AA. It was concluded that the chronic AA- deficient state in ODS rats played an insignificant role in oral carci nogenesis and that other factors, for example, genetic differences in susceptibility to NQO, contributed to the present findings.