EFFECT OF EXCESS DIETARY IRON ON THE PROMOTION STAGE OF 1-METHYL-1-NITROSOUREA-INDUCED MAMMARY CARCINOGENESIS - PATHOGENETIC CHARACTERISTICS AND DISTRIBUTION OF IRON

The effect of feeding a 10-fold excess of dietary iron on the promotio n stage of MNU-induced mammary carcinogenesis was investigated. Rats f ed excess iron in the diet had more mammary carcinomas than rats fed t he recommended level of iron. A significantly greater proportion of ca rcinomas in rats fed the excess iron diet had the normal Ha-ras gene r ather than the mutated form (G-->A transition mutation in codon 12). I n non-tumor bearing rats, mammary epithelial cells in lobules were the primary site of iron accumulation. However, in mammary carcinomas, a shift in the distribution of iron from the epithelial cells to the str oma was noted. Iron was predominantly found in tumor stroma; malignant epithelial cells failed to accumulate comparable levels of iron. Thes e observations indicate that in the presence of excess iron there is a n increase in the number of mammary carcinomas that do not bear the mu tant Ha-ras gene. Whether changes in the distribution of iron within t he mammary gland contribute to the altered pathogenetic characteristic s of these tumors is being investigated.