Promoting effects of milk on the development of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors in rats

Abstract

To assess the effect of milk on the development of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors, 48 female Sprague-Dawley rats treated with DMBA were divided into 3 groups and given 1 of 3 test solutions for 20 weeks as their drinking liquid: milk, estrone sulfate solution or tap water. The milk group showed a significantly great incidence (75%) in tumor development compared with the water group (38%) and was comparable to the estrone sulfate group (69%). Mean tumor number per rat in the milk group was significantly higher than that in the water group (p=0.009). We classified the mammary tumors into three histological types: intraductal papilloma, fibroadenoma, and adenocarcinoma. Although the percent of intraductal papilloma and fibroadenoma was almost same among the three groups, malignant tumor was found only in the milk and estrone sulfate groups. In conclusion, our results indicate that milk as well as estrone sulfate promotes the development of DMBA-induced mammary tumors in rat and could be associated with the occurrence of adenocarcinoma.

Fig. 1

HE staining of rat mammary tumor. A) Intraductal papilloma. Numerous papillary projections sustained by thin connective tissue cores can be seen. HE×25. B) Fibroadenoma. Fibrous stroma is compressing the tubular alveolar components. HE×25. C) Adenocarcinoma. Numerous secondary lumina can be seen. HE×25.

Fig. 2

Immunostaining for SMA. A) Immunoperoxidase reaction with anti-alpha smooth muscle actin antibody reveals myoepithelial cells lining nests of secretory cells in intraductal papilloma. Nuclei counterstained with HE×100. B) Immunoperoxidase reaction with anti-alpha smooth muscle actin antibody reveals that myoepithelial cells scattered at the base of nests in fibroadenoma. Nuclei counterstained with HE×100. C) Immunoperoxidase reaction with anti-alpha smooth muscle actin antibody reveals that myoepithelial cells scattered at the base of nests and stretched in adenocarcinoma. Nuclei counterstained with HE×100.

Fig. 3

Immunostaining for ER. Nuclear staining indicates immunoreactive ER. Nuclei counterstained with HE. A) Intraductal papilloma, B) Fibroadenoma, C) Adenocarcinoma. ×100.

Fig. 4

Immunostaining for PCNA. Nuclear staining indicates immunoreactive PCNA. Nuclei counterstained with haematoxylin. A) Intraductal papilloma. PCNA labeling index is low. B) Fibroadenoma. PCNA labeling index is moderate. C) Adenocarcinoma. PCNA labeling index is high. ×100.