Inhibition of 4-nitroquinoline-1-oxide-induced rat tongue carcinogenesis by the naturally occurring plant phenolics caffeic, ellagic, chlorogenic and ferulic acids

The modifying effects of dietary administration of the plant phenolic antioxidants caffeic acid (CA), ellagic acid (EA), chlorogenic acid (CGA) and ferulic acid (FA) during the initiation phase on 4-nitroquinoline-1-oxide (4-NQO)-induced tongue carcinogenesis and on the number and area of silver-stained nucleolar organizer region proteins (AgNORs), a new cell proliferation marker, of the tongue squamous epithelium were investigated in male F344 rats. Rats were fed the diet containing 500 p.p.m. CA, 400 p.p.m. EA, 250 p.p.m. CGA or 500 p.p.m. FA for 7 weeks. One week after the commencement of the diets, 4-NQO (20 p.p.m.) was administered in the drinking water for 5 weeks. Feeding of four phenolic compounds significantly reduced the incidences of tongue neoplasms (squamous cell papilloma and carcinoma) and preneoplastic lesions (hyperplasia and dysplasia) by 32 weeks, and rats fed CA or EA had no tongue neoplasms. The number and area of AgNORs per nucleus were decreased significantly by dietary treatment with these four phenolics. Thus, CA, EA, CGA and FA inhibited the tongue carcinogenesis induced by 4-NQO when they were administered concurrently with the carcinogen. These results might suggest possible application of these natural substances for cancer chemoprevention in tongue in addition to other tissues (skin, lung, liver and esophagus).