Effects of Organoselenium Compounds on Induction of Mouse Forestomach Tumors by Benzo(a)pyrene

The selenium analogues of three known inhibitors of chemical carcinogenesis were synthesized and the compounds were tested for their ability to inhibit the induction of forestomach tumors in mice by benzo(a)pyrene. Groups of female CD-1 mice were given NIH-07 diet, or NIH-07 diet to which one of the following test compounds had been added: p-methoxyphenol (30 μmol/g diet and 3.3 μmol/g diet); p-methoxybenzeneselenol (3.3 μmol/g diet); benzylthiocyanate (0.045 μmol/g diet); benzylselenocyanate (0.045 μm\o\/g diet); phenothiazine (3.8 μmol/g diet); and phenoselenazine (3.8 μmol/g diet). The test compounds were administered for 1 week prior to treatment with benzo(a)pyrene, during the 4 weeks of benzo(a)pyrene treatment, and for 1 week after benzo(a)pyrene treatment. Twelve weeks later the mice were sacrificed and forestomach tumors were counted and confirmed histologically as papillomas, p-Methoxyphenol was the most effective inhibitor and was the only one which significantly reduced both the percentage of tumor-bearing animals and the number of forestomach tumors per animal. At the 3.3-/imol/g diet, p-methoxyphenol reduced the number of tumors per animal from 3.3 to 0.8 (P < 0.0003). p-Methoxybenzeneselenol reduced the number of tumors per animal from 3.3 to 2.0 (P < 0.05). Benzylthiocyanate showed no significant inhibitory effect, but benzylselenocyanate reduced the number of tumors per animal from 3.3 to 1.7 (P < 0.01). Phenothiazine significantly enhanced the number of tumors per animal from 3.3 to 6.5 (P < 0.004). Phenoselenazine had no effect on tumor induction. The results of this study indicate that two synthetic organoselenium compounds, p-methoxybenzeneselenol and benzylselenocyanate, are effective inhibitors of mouse forestomach tumorigenesis induced by benzo(a)pyrene.