Modifying effects of phytic acid and gamma-oryzanol on the promotion stageof rat carcinogenesis

The modifying effects of phytic acid and gamma-oryzanol on the promotion st age of carcinogenesis were investigated using several two stage carcinogene sis model sin rates. In a multi-organ carcinogenesis mode, male F344 rats w ere given combined treatment with 2,2'-dihydroxy-di-n-propylnitrosamine (DH PN) N-ethyl-N-hydroxyethylnitrosamine (EHEN) and 3,2'-dimethyl-4-aminobiphe nyl (DMAB) during the initial 3 weeks as initiators, and then treated with dietary 2% phytic acid (50% in water), 1% gamma-oryzanol or basal diet alon e for 32 weeks. Although the appearance of hepatic tumors was suppressed, t he incidence of urinary bladder papillomas was increased by phytic acid. In addition, the incidence and multiplicity of lung tumors were significantly increased by gamma-oryzanol. Esophagus, colon, pancreas, kidney and thyroi d lesion development was not influenced by these compounds. In a gamma-oryz anol dose response experiment using DHPN in the drinking water as an initia tor, enhancing effects on lung were observed at a dose of 1% but not at 0.5 % or lower, When th modifying effects of phytic acid, and its sodium (Na-PA ), potassium (K-PA) and magnesium (Mg-PA) alt were further examined in rats pretreated with the bladder carcinogen N-butyl-N-(4-hydroxybutyl)nitrosami ne (BBN), a clear increase in the incidences of bladder tumors was noted, w ith only Na-PA, phytic acid itself being without effect. Finally, examinati on of the modifying potential of phytic acid and gamma-oxyzanol on mammary carcinogenesis in female Sprague Dawley rats pretreated with a single intra gastric dose of 7,12-dimethylbenz(a)anthracene (DMBA) revealed no significa nt differences in the final incidences and multiplicities of mammary tumors , but the average tumor diameter was significantly reduced and the average survival time was increased with phytic acid gamma-Oryzanol tended to decre ase the size of the tumor brit without significant difference. These result s indicate that phytic acid inhibits hepatic and mammary carcinogenesis, wh ile its Na-salt is a promoter of bladder carcinogenesis. The effect of phyt ic acid itself oil urinary bladder carcinogenesis is equivocal. gamma-Oryza nol is a promoter of lung carcinogenesis but ifs effect is weak and exerted only at a very high dose level.