1,4-PHENYLENEBIS(METHYLENE)SELENOCYANATE EXERTS EXCEPTIONAL CHEMOPREVENTIVE ACTIVITY IN RAT TONGUE CARCINOGENESIS

Among the organoselenium compounds, 1,4-phenylenebis(methylene) seleno cyanate (p-XSC) is reported to exert the most effective chemopreventiv e effect on chemically induced carcinogenesis in the mammary glands, c olon, and lung of laboratory animals. This study was designed to test the inhibitory effects of dietary p-XSC (5 and 15 ppm as selenium) dur ing the initiation phase (1 week: before, during, and up to 1 week aft er the carcinogen exposure) and the postinitiation phase (1 week after carcinogen administration until termination) on the formation of neop lasms of the tongue induced in male F344 rats by 4-nitroquinotine-1-ox ide (4-NQO). The doses of p-XSC were 20% (5 ppm selenium) and 60% (15 ppm selenium) of maximum tolerated dose levels. At 6 weeks of age, all rats except those given p-XSC alone and those in untreated groups wer e treated with 4-NQO (20 ppm in the drinking crater for 8 weeks). Diet ary p-XSC, administered at selenium levels of 5 and 15 ppm during eith er the initiation or postinitiation phases, significantly reduced the incidence of carcinoma of the tongue. p-XSC was especially effective w hen it was administered at 15 ppm selenium during the postinitiation p hase, in which case it completely inhibited the development of tongue carcinoma (from 47% in the dietary control to 0%). Glutathione S-trans ferase activities in tbe liver and tongue of rats treated with 4-NQO a nd p-XSC were significantly elevated compared to those in rats treated with 4-NQO alone. Similarly, quinone reductase activity was significa ntly elevated in the liver but decreased in the tongue (posterior port ion). Such modulation by p-XSC in the phase II enzyme activities of th e liver and tongue might be related to inhibition of the initiation. I n addition, the expression of cell proliferation biomarkers, such as p olyamine level, ornithine decarboxylase activity, 5-bromodeoxyuridin-l abeling index, and argyrophilic nucleolar organizer's protein number, in the epithelium of the tongue was significantly reduced in rats that were fed the p-XSC diets compared to those who were fed the basal die t. Such alteration in cell proliferation through modulation of ornithi ne decarboxylase activity and polyamine biosynthesis in the tongue epi thelium might be related to inhibition occurring in the postinitiation phase of carcinogenesis. The dose levels of p-XSC used induced no tox icity or alteration in body weight gain. Although the precise mechanis ms of p-XSC-induced inhibition of tongue carcinogenesis remains to be elucidated it is evident that p-XSC has powerful chemopreventive effic acy against tongue carcinogenesis.