Effects of dietary fat and alpha-tocopherol on gamma-glutamyltranspeptidase activity of 7, 12-dimethylbenz(alpha)anthracene-induced mammary gland adenocarcinomas.

The levels of gamma-glutamyltranspeptidase (GGTP) (EC 2.3.2.2) were measured in 7, 12-dimethylbenz(alpha)anthracene-induced mammary adenocarcinomas, in control mammary gland tissue and in sera from tumor-bearing and control rats. The carcinogenic process was modulated by diets differing in the type and amount of fat with and without alpha-tocopherol supplementation. Rat mammary adenocarcinomas showed significantly elevated (up to 25-fold) levels of GGTP when compared with adjacent histologically-uninvolved tissue or with mammary tissue of control rats. GGTP activity in sera from tumor-bearing rats was also elevated up to 4-fold than in the corresponding controls. Histochemical studies of the frozen section of mammary adenocarcinomas indicated that GGTP was localized in neoplastic ductal epithelial cells. In tumor rats on alpha-tocopherol supplemented diets, GGTP activity in the adenocarcinomas was mainly in the particulate (membrane-bound) fraction. In contrast, the tumor rats receiving alpha-tocopherol-deficient diets, the total GGTP activity was distributed in both particulate and cytosolic fractions, suggesting an altered membrane-GGTP interaction. The levels of GGTP in control mammary gland and sera of control rats from the low fat dietary groups were up to 7-fold higher than the corresponding control values in either of two high-fat groups. These high levels of GGTP in the serum and tissues of animals from the low fat dietary group are consistent with lower tumor incidence through enhanced carcinogen detoxification.