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 promotion stage of MNU-induced mammary carcinogenesis was investigated. Rats fed excess iron in the diet had more mammary carcinomas than rats fed the recommended level of iron. A significantly greater proportion of carcinomas in rats fed the excess iron diet had the normal Ha-ras gene rather than the mutated form (G-->A transition mutation in codon 12). In 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 stroma was noted. Iron was predominantly found in tumor stroma; malignant epithelial cells failed to accumulate comparable levels of iron. These observations indicate that in the presence of excess iron there is an increase in the number of mammary carcinomas that do not bear the mutant Ha-ras gene. Whether changes in the distribution of iron within the mammary gland contribute to the altered pathogenetic characteristics of these tumors is being investigated.