The effects of high dietary fat and indomethacin on 7,12-dimethylbenz(a)anthracene-induced mammary carcinomas in rats

The effects of high dietary fat and indomethacin (IND) on tumorigenesis, tumor growth, tumor histology, cell kinetics and receptor contents of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinomas were investigated in Sprague-Dawley (S-D) rats. Tumorigenesis was stimulated by high dietary fat and inhibited by IND. However, both high dietary fat and IND stimulated tumor growth. Switching the animals from the high-fat diet with or without IND to the low-fat diet suppressed tumor growth and affected the cell kinetics. Histologically, the tumors showed a dense proliferation of ductal cells in the high-fat alone or IND-treated high-fat diet group. Tumors in the low-fat or IND-treated low-fat group, as well as the group switched from a high-fat or IND-treated high-fat diet to a low-fat diet, demonstrated well-developed glandular structures. The estrogen receptor and progesterone receptor contents were not different between the groups either prior to or following switching diets. Therefore, high dietary fat stimulates tumorigenesis and tumor proliferation, while IND has dual effects: a stimulating effect on tumor proliferation, but an inhibiting effect on tumorigenesis. It also appears that hormone-receptor status does not play an important role in the stimulatory effects of high-fat diet or IND on tumor proliferation.