The modifying effects of
phytic acid and
gamma-oryzanol on the promotion stage of
carcinogenesis were investigated using several two stage
carcinogenesis models in rats. In a multi-organ
carcinogenesis model, male F344 rats were given combined treatment with
2,2'-dihydroxy-di-n-propylnitrosamine (
DHPN),
N-ethyl-N-hydroxyethylnitrosamine (EHEN) and
3,2'-dimethyl-4-aminobiphenyl (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 alone for 32 weeks. Although the appearance of hepatic
tumors was suppressed, the 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 thyroid lesion development was not influenced by these compounds. In a
gamma-oryzanol dose response experiment using
DHPN in the
drinking water as an initiator, enhancing effects on lung were observed at a dose of 1% but not at 0.5% or lower. When the modifying effects of
phytic acid, and its
sodium (Na-PA),
potassium (K-PA) and
magnesium (Mg-PA)
salt were further examined in rats pretreated with the bladder
carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), a clear increase in the incidences of
bladder tumors was noted, with only Na-PA,
phytic acid itself being without effect. Finally, examination of the modifying potential of
phytic acid and gamma-oxyzanol on mammary
carcinogenesis in female Sprague Dawley rats pretreated with a single intragastric dose of
7,12-dimethylbenz(a)anthracene (DMBA) revealed no significant 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 decrease the size of the
tumor but without significant difference. These results indicate that
phytic acid inhibits hepatic and mammary
carcinogenesis, while its Na-
salt is a promoter of bladder
carcinogenesis. The effect of
phytic acid itself on urinary bladder
carcinogenesis is equivocal.
gamma-Oryzanol is a promoter of lung
carcinogenesis but its effect is weak and exerted only at a very high dose level.