Induction by 4‐nitroquinoline‐l‐oxide of oral epithelial dysplasia and neoplasia in scurvy‐prone osteogenic disorder shionogi (ODS) rats

Abstract

Carcinogenesis by 4‐nitroquinoline‐l‐oxide (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 development. 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 unable to synthesize AA and requires supplementation for its survival. This study examined the effects of NQO on the oral mucosa of ODS and outbred Wistar rats. NQO (0.5%) was applied topically to the palatal mucosa 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 0.33 g/l AA. Vehicle‐treated and untreated control animals were included. The rats were killed two weeks after the final NQO application, and the tissues were examined. Epithelial dysplasia was assessed using a modified 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 indicated that the oral mucosa of the ODS and outbred rats were susceptible 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 ≤ 0.05). No significant difference was found in the dysplasia scores and in the rate of OMSCC development between ODS rats given 2.5 g/l of AA and ODS rats given 0.33 g/l of AA (p > 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 μM for the outbred rats, 8±1 μM for the ODS rats given 0.33 gll AA supplementation, and 29 ±2 μM for the ODS rats given 2.5 gll AA. It was concluded that the chronic AA‐deficient state in ODS rats played an insignificant role in oral carcinogenesis and that other factors, for example, genetic differences in susceptibility to NQO, contributed to the present findings.