Abstract
In 1936 Kenosita demonstrated that feeding a diet containing 4-dimethylaminoazoben-zene (DAB) caused the production of hepatomas in the rat. Five years later, Kensler et al. (1) showed that excess riboflavin provided such experimental rats with protection against the action of this dye and this observation appears to have been the first evidence suggesting that nutrition might play a role in carcinogenesis. The in vitro activity of a liver azo reductase enzyme is enhanced by the addition of excess riboflavin (2, 3) and the administration of DAB causes a decrease in the ability of this enzyme to cleave DAB (4, 5). The evidence that this enzyme is a flavoprotein has not been convincing.
Morris and Robertson (6) found that the growth rate of mammary carcinomas in C3H mice was decreased by severe riboflavin deficiency. Holly et al. (7) reported that the riboflavin analog 6,7-dichloro-9-(1′-D-sorbityl)-isoalloxazine, which has no antiriboflavin activity in rats, caused regression of established lymphosarcoma in mice.
More recently Kim et al. (8) showed that 7-ethyl-8-methyl-10-(D-ribityl) isoalloxazine (7-Et-flavin), a homolog of riboflavin, specifically inhibited the growth rate of Walker rat carcinoma 256. The latter compound is not a riboflavin antagonist in any test system tried; it is able to serve as the sole flavin for Lactobacillus casei and for the rat (9). While an isomer of the above 7-Et-flavin, namely 7-methyl-8-ethyl-10-(D-ribityl) isoalloxazine (8-Et-flavin) is nearly as potent a replacement of riboflavin for the rats as 7-Et-flavin, it exerted no inhibitory action on the growth rate of the Walker carcinoma.
At the cellular level, in the liver of the rat, a striking effect of the activities of these two homologs is observed.
Get full access to this article
View all access options for this article.