The effect of rice diets on the formation of induced and spontaneous hepatomas in mice.

By 1935, various investigators (9) principally Kinosita and his co-workers had established the hepato-carcinogenic activity of o-aminoazotoluene and N,N-dimethyl-p-aminoazobenzene. These azo dyes, administered in the diet or by subcutaneous injection, elicit changes--including neoplasms--in the livers of rats and mice and perhaps in the livers of other species. Subsequently it was established that in the rat the formation of hepatomas induced by o-aminoazotoluene or p-dimethylaminoazobenzene is strikingly dependent on the quality of the diet. For example, dried brewer's yeast (27, 5) or liver (18, 19) added in suitable amounts to a rice diet effectively inhibit, in comparison with an unsupplemented rice diet, the formation of liver cancer in rats being fed either of these azo dyes. The investigations of Sugiura and Kensler (26), of Rusch and associates (16, 22), and of others, employing diets consisting wholly or in part of purified food stuffs such as casein, crystalline B vitamins, etc., have led to the conclusion that diets containing high levels of protein and riboflavin protect against the toxic and carcinogenic action of p-dimethylaminoazobenzene in rats. The protective action of dried yeast or liver is generally attributed to their high content of protein and riboflavin. The present studies with mice were initiated to determine whether in this species also the quality of the diet influences the formation of hepatomas, either induced by an azo dye or occurring spontaneously. Four experiments were performed: Hepatomas were induced by o-aminoazotoluene in three of the experiments. In the fourth, the spontaneous hepatoma was studied; that is, a mouse strain in which hepatomas form without exposure to a known carcinogen was employed, and no azo dye was administered. Dba strain mice were used in the experiments on induced hepatomas; spon-