Effect of dietary vitamin A or N-acetylcysteine on ethylnitrosourea-induced rat gliomas

It is our hypothesis that low grade gliomas are the glial counterparts of o ther precancerous lesions such as colon polyps and, therefore, suitable tar gets for chemoprevention. Steps in the molecular progression of gliomas hav e been described, indicating that an accumulation of abnormalities is requi red for progression to a high grade and interruption of this progression mi ght be possible. An animal model of chemical glial carcinogenesis was used to test this hypothesis. Pregnant rats were injected intravenously with ENU (ethylnitrosourea) on the 18th day of gestation to induce gliomas in the o ffspring, which were randomized to receive control diet, diet supplemented with vitamin A palmitate, or diet supplemented with N-acetylcysteine. Anima ls exposed to ENU and receiving a control diet developed brain tumors and h ad a shortened life expectancy compared with rats unexposed to ENU. The ani mals treated with NAC showed no statistically significant delay in the time to tumor and no change in the histologic grade of the tumors when compared with animals receiving control diet, but the time to death from any cause of NAC treated animals differed significantly from untreated animals. Anima ls receiving high dose VA had statistically significantly prolonged time to tumor, survived significantly longer than untreated animals, but had no re duction in the total number of tumors or change in the histologic grade of their tumors. The theoretical basis of these results is likely due to the p utative mechanism of action of these agents. These data indicate that gliom a chemoprevention is possible and deserves further exploration.