Singh M, Lu J, Briggs S P, McGinley J N, Haegele A D, Thompson H J
Division of Laboratory Research, AMC Cancer Research Center, Denver, CO 80214.
Carcinogenesis. 1994 Aug;15(8):1567-70. doi: 10.1093/carcin/15.8.1567.
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.
研究了给予过量10倍膳食铁对N-甲基-N-亚硝基脲（MNU）诱导的乳腺癌发生促进阶段的影响。饮食中摄入过量铁的大鼠比摄入推荐铁水平的大鼠患更多的乳腺癌。在摄入过量铁饮食的大鼠中，有显著更高比例的癌具有正常的Ha-ras基因而非突变形式（密码子12处的G→A转换突变）。在未患肿瘤的大鼠中，小叶中的乳腺上皮细胞是铁积累的主要部位。然而，在乳腺癌中，注意到铁的分布从上皮细胞转移到了基质。铁主要存在于肿瘤基质中；恶性上皮细胞未能积累相当水平的铁。这些观察结果表明，在存在过量铁的情况下，不携带突变型Ha-ras基因的乳腺癌数量增加。乳腺内铁分布的变化是否导致这些肿瘤的致病特征改变正在研究中。
