Research Studying the Effect of Soybean Diets on Mammary Tumors in Rats
Compiled by Debbie “The Rat Lady” Ducommun
Most of the research done on the influence of diets containing soybean protein on the development of mammary tumors in rats has been done on mammary tumors experimentally induced in the rats. A chemical called methylnitrosourea (MNU) reliably produces cancerous mammary tumors in rats when injected. So does radiation with x-rays. These rats can then be used to test various ways to treat or prevent the tumors. These studies can be done in a matter of weeks, while doing the same studies on spontaneous mammary tumors would require at least 2 or more years, since most rats don’t start growing natural mammary tumors until they are at least 18-24 months old. In addition, because most of these studies are interested in finding a treatment or prevention of mammary cancer in humans, the rats with induced mammary cancer provide a better model than rats with spontaneous mammary tumors, most of which are benign and not cancerous.
However, a few studies have shown that the same factors that tend to reduce the formation or growth of induced mammary tumors, also tend to reduce the formation of spontaneous tumors. The first two studies listed here mention spontaneous tumors.
Soybean diet lowers breast tumor incidence in irradiated rats, Troll, W. et al. Carcinogenesis 1980; 1: 469-72
This paper examines the relationship between feeding a diet rich in protease inhibitors and the reduction of mammary cancer induced by x-irradiation in Sprague-Dawley rats. Of a total of 145 irradiated animals, 44% of the 45 rats fed a raw soybean diet containing a high concentration of protease inhibitor developed mammary tumors as compared to 74% of 50 rats fed a casein diet containing no protease inhibitor. Animals fed Purina rat chow which contained low levels of protease inhibitor exhibited a 70% mammary tumor incidence. No spontaneous neoplasms were found in any of the non-irradiated animals on the raw soybean diet whereas about 10% of the animals on the protease-free diet developed tumors. (emphasis added) Thus, soybeans which are rich in protease inhibitors reduced the induction of mammary cancer in x-irradiated rats. This work suggests that diets rich in protease inhibitors may contribute to reducing cancer incidence in man.
Troll, W. Soybean diet lowers breast tumor incidence in irradiated rats.
Soy and Whey Proteins Downregulate DMBA-Induced Liver and Mammary Gland CYP1 Expression in Female Rats. J. Craig Rowlands, Ling He, Reza Hakkak, Martin J. J. Ronis and Thomas M. Badger. Journal of Nutrition. 2001;131:3281-3287.
From the Discussion section:
Previous studies have reported that the incidence of either spontaneous mammary tumors
23. Troll, W., Belman, S., Wiesner, R. & Shellabarger,
C. J. (1979) Protease action in
carcinogenesis. Holzer, H. Tschasche,
H. eds. Biological Function of Proteinases 1979:165-170
Other studies cited in this article included the following:
24. Barnes, S., Grubbs, C., Setchell, K. D. & Carlson, J. (1990) Soybeans inhibit mammary tumors in models of breast cancer. Prog. Clin. Biol. Res. 347:239-253.[Medline]
27. Zaizen, Y., Higuchi, Y., Matsuo, N., Shirabe, K., Tokuda, H. & Takeshita, M. (2000) Antitumor effects of soybean hypocotyls and soybeans on the mammary tumor induction by N-methyl-n-nitrosourea in F344 rats. Anticancer Res 20:1439-1444.[Medline]
28. Gotoh, T., Yamada, K., Yin, H., Ito, A., Kataoka, T. & Dohi, K. (1998) Chemoprevention of N-nitroso-N-methylurea-induced rat mammary carcinogenesis by soy foods or biochanin A. Jpn. J. Cancer Res. 89:137-142.[Medline]
In utero exposure to maternal diets containing soy protein isolate, but not genistein alone, protects young adult rat offspring from NMU-induced mammary tumorigenesis, Ying Su, Renea R. Eason, Yan Geng, SR Till, Thomas M. Badger and Rosalia C.M. Simmen, Carcinogenesis, 2007 28(5):1046-1051.
This has exciting implications! It means that mother rats fed a diet high in soybean protein might have daughters less likely to have mammary tumors.
Abstract (Full text online):
The linkage of nutrition and cancer prevention is an
intriguing concept that is gaining widespread support. Here, we
investigated the influence of developmental context on dietary
protection against tumorigenesis initiated
by the direct-acting carcinogen N-methyl-N-nitrosourea (NMU), and examined potential mechanisms underlying
these effects. Rats were exposed only in utero
or for lifetime to American Institute of Nutrition-93G diets made
with casein (
chemotherapeutic potentials upon MNU induced mammary carcinomas (MCA) by a
combination of miso and tamoxifen.
Ito, A. et al. Research Inst. Of Radiation Biology and
Aim: A single administration of either miso (fermented soybean paste), soybean, or biochanin A (isoflavone) was quite inhibitory for the occurrence of rat MCA induced by MNU. The present study was undertaken to evaluate a combination effect of miso and tamoxifen for the 1) primary prevention of MNU induced mammary tumors, and 2) chemo-therapeutic trials for manifested MNU induced mammary tumors (1.5 to 2.0 cm in average size). Results: 1. Continuous administration of either miso or tamoxifen in rats treated with MNU was significantly inhibitory for the occurrence of mammary carcinomas. 2. a combinational treatment of miso and tamoxifen was almost completely inhibitory for the occurance of MCA. 3. Averaged sizes of 1.5 to 2.0 cm mammary tumors were treated with a combination of tamoxifen and 2%, 5%, or 10% miso containing diet, and growth of MCA was reduced dose dependently with the % of miso. 4. Possible preventive mechanisms of miso for the development of mammary tumors could be explained by the findings: 1) up-regulation of estrogen receptor levels of MCA, and 2) immunological reactions around MCA tissues treated with miso diet.
A combined effect of tamoxifen and miso for the
development of mammary tumors induced with MNU in SD rats. Ito, A. et al. Research Inst. For
Radiation Biol. & Med.,
(* significant from control by p<0.05, **significant from control by p<0.01)
Isolate and Methionine Supplementation Affect Mammary
Tumor Progression in Rats, E. J. Hawrylewicz, H. H. Huang and W. H. Blair, The Journal of Nutrition, Manuscript received 30 October 1990.
The effect of feeding soybean protein isolate (
Chemoprevention of DMBA-induced mammary cancer in rats by dietary soy.
Gallo, D, et al. Breast Cancer Res Treat.2001 Sep;69(2):153-64.
This study was designed to assess the potential chemopreventive effect of the administration of a standardized soy extract, SOYSELECT, on 7,12-Dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in rats. Three groups, 24 females each, were used. Animals were fed either a phytoestrogen-free diet alone (control) or the same diet supplemented with 0.35% or 0.7% of soy extract. Treatment started at weaning and continued to the end of the study (24 weeks after DMBA administration). At day 50 of age all animals received via oral gavage 80 mg/kg DMBA. Only tumors subsequently classified as adenocarcinomas were considered for data evaluation. In rats on the soy diet, mammary tumors took a longer period of time to develop as compared to control rats. However, at the end of the study, no relevant difference in tumor incidence and multiplicity was observed among the groups. The most significant changes were seen between control and soy-treated groups when tumor dimension and results from histopathologic examination were considered. The latter, in fact, showed a dose-dependent reduction in the percentage of poorly differentiated tumors in treated animals. This change was statistically significant in animals receiving 0.7% soy. In addition, assessment of estrogen and progesterone receptor (ERalpha, PR) levels, revealed a significant reduction in the percentage of ERalpha and PR positive tumors in animals receiving 0.7% dietary soy, when compared to controls. Interestingly, genistein and daidzein plasma levels determined at the end of the study were within the range of those detected in people consuming large amounts of soyfoods.
The effect of soybean protein, low methionine, diet on the histopathology of recurrent mammary
tumors. E.J. Hawrylewicz,
W.H. Blair, J.J. Zapata, H.H. Huang, Mercy Hospital and Medical Center,
Chicago, IL, Presented at the First International Symposium on the role of Soy
in Preventing and Treating Chronic Disease,
We reported that a soybean protein (
Inhibitory effects of Bifidobacterium-fermented soy milk on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced rat mammary carcinogenesis, with a partial contribution of its component isoflavones. Toshihisa Ohta, et al. Carcinogenesis, Vol. 21, No. 5, 937-941, May 2000
High consumption of soybean and soybean-related products is
hypothesized to contribute to protection against breast cancer. Soybean
is a rich source of genistein, a putative cancer chemopreventive agent. Fermented soy milk (