Modifying effects of phytic acid and gamma-oryzanol on the promotion stage of rat carcinogenesis.
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.
Hirose
M
M
Division of Pathology, National Institute of Health Sciences, Tokyo, Japan. m-hirose@nihs.go.jp
Fukushima
S
S
Imaida
K
K
Ito
N
N
Shirai
T
T
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002085:Butylhydroxybutylnitrosamine / Q000633:toxicity; D004052:Diethylnitrosamine / Q000031:analogs & derivatives / Q000633:toxicity; D005260:Female; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008297:Male; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D009602:Nitrosamines / Q000633:toxicity; D010666:Phenylpropionates / Q000494:pharmacology*; D010833:Phytic Acid / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley
D016588:Anticarcinogenic Agents; D000960:Hypolipidemic Agents; D009602:Nitrosamines; D010666:Phenylpropionates; C023845:N-ethyl-N-hydroxyethylnitrosamine; D002085:Butylhydroxybutylnitrosamine; D004052:Diethylnitrosamine; C012457:diisopropanolnitrosamine; D015127:9,10-Dimethyl-1,2-benzanthracene; D010833:Phytic Acid; C013172:gamma-oryzanol