© 1996 Oxford University Press
research-article |
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION: Prepubertal genistein exposure suppresses mammary cancer and enhances gland differentiation in rats
Department of Pharmacology and Toxicology, University of Alabama at Birmingham Birmingham, AL 35294–0019. USA
1To whom correspondence should be addressed
Genistein, a component of soy, was administered to pre-pubertal female Sprague-Dawley CD rats and investigated for chemoprevention against mammary cancer. Genistein, at 500 µg/g body wt or an equivalent volume of the vehicle, dimethylsulfoxide (DMSO), was injected (s.c) on days 16, 18 and 20 post-partum. At day 50 post-partum all animals were exposed to 80 µg dimethylbenz[a]anthracene (DMBA) per g body wt. Animals treated prepubertally with genistein as compared to DMSO had reduced incidence and significantly fewer adenocarcinomas per animal. Mammary whole mount analysis showed that prepubertal genistein treatment resulted in mammary glands of 50-day-old rats developing fewer terminal end buds and more lobules II. Cell proliferation studies with bromodeoxyuridine (BrdU) showed that terminal end buds from mammary glands of 50-day-old females treated prepubertally with genistein had significantly fewer cells in S-phase of the cell cycle. Serum genistein concentrations in 21- and 50-day-old females following prepubertal genistein treatment were 4.2 ± 0.6 µM and 102 ± 30 nM, respectively. Animals treated prepubertally with genistein as compared to vehicle spent more time in the estras phase of the estrus cycle, although all animals did cycle. In 50-day-old females, circulating estradiol-17ß and progesterone concentrations were not significantly altered by the prepubertal genistein treatment Oocyte/follicle counts and numbers of atretic follicles and corpora lutea were not significantly different between the genistein- and vehicle-treated animals. We conclude that genistein treatment during the prepubertal period can suppress the development of chemically-induced mammary cancer without significant toxicity to the endocrine/reproductive system.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. A. Korde, A. H. Wu, T. Fears, A. M.Y. Nomura, D. W. West, L. N. Kolonel, M. C. Pike, R. N. Hoover, and R. G. Ziegler Childhood Soy Intake and Breast Cancer Risk in Asian American Women Cancer Epidemiol. Biomarkers Prev., April 1, 2009; 18(4): 1050 - 1059. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Mardon, J. Mathey, S. Kati-Coulibaly, C. Puel, M.-J. Davicco, P. Lebecque, M.-N. Horcajada, and V. Coxam Influence of Lifelong Soy Isoflavones Consumption on Bone Mass in the Rat Experimental Biology and Medicine, February 1, 2008; 233(2): 229 - 237. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Lampe, Y. Nishino, R. M. Ray, C. Wu, W. Li, M.-G. Lin, D. L. Gao, Y. Hu, J. Shannon, H. Stalsberg, et al. Plasma Isoflavones and Fibrocystic Breast Conditions and Breast Cancer Among Women in Shanghai, China Cancer Epidemiol. Biomarkers Prev., December 1, 2007; 16(12): 2579 - 2586. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.B. Moore, L. Castro, L. Yu, X. Zheng, X. Di, M.I. Sifre, G.E. Kissling, R.R. Newbold, C.D. Bortner, and D. Dixon Stimulatory and inhibitory effects of genistein on human uterine leiomyoma cell proliferation are influenced by the concentration Hum. Reprod., October 1, 2007; 22(10): 2623 - 2631. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Duffy, K. Perez, and A. Partridge Implications of Phytoestrogen Intake for Breast Cancer CA Cancer J Clin, September 1, 2007; 57(5): 260 - 277. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. R. Thomsen, K. Almstrup, J. E. Nielsen, I. K. Sorensen, O. W. Petersen, H. Leffers, and V. M. Breinholt Estrogenic Effect of Soy Isoflavones on Mammary Gland Morphogenesis and Gene Expression Profile Toxicol. Sci., October 1, 2006; 93(2): 357 - 368. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Padilla-Banks, W. N. Jefferson, and R. R. Newbold Neonatal Exposure to the Phytoestrogen Genistein Alters Mammary Gland Growth and Developmental Programming of Hormone Receptor Levels Endocrinology, October 1, 2006; 147(10): 4871 - 4882. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E. Wood, S. E. Appt, T. B. Clarkson, A. A. Franke, C. J. Lees, D. R. Doerge, and J. M. Cline Effects of High-Dose Soy Isoflavones and Equol on Reproductive Tissues in Female Cynomolgus Monkeys Biol Reprod, September 1, 2006; 75(3): 477 - 486. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A Franke, B. M Halm, L. J Custer, Y. Tatsumura, and S. Hebshi Isoflavones in breastfed infants after mothers consume soy. Am. J. Clinical Nutrition, August 1, 2006; 84(2): 406 - 413. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Fenton Endocrine-Disrupting Compounds and Mammary Gland Development: Early Exposure and Later Life Consequences Endocrinology, June 1, 2006; 147(6): s18 - s24. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-J. Wang, E. Bartolucci-Page, S. E. Fenton, and L. You Altered Mammary Gland Development in Male Rats Exposed to Genistein and Methoxychlor Toxicol. Sci., May 1, 2006; 91(1): 93 - 103. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Rowell, D. M. Carpenter, and C. A. Lamartiniere Chemoprevention of Breast Cancer, Proteomic Discovery of Genistein Action in the Rat Mammary Gland J. Nutr., December 1, 2005; 135(12): 2953S - 2959S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L Hilakivi-Clarke, C Wang, M Kalil, R Riggins, and R G Pestell Nutritional modulation of the cell cycle and breast cancer Endocr. Relat. Cancer, December 1, 2004; 11(4): 603 - 622. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. D. Allred, K. F. Allred, Y. H. Ju, T. S. Goeppinger, D. R. Doerge, and W. G. Helferich Soy processing influences growth of estrogen-dependent breast cancer tumors Carcinogenesis, September 1, 2004; 25(9): 1649 - 1657. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. O. Mueller, S. Simon, K. Chae, M. Metzler, and K. S. Korach Phytoestrogens and Their Human Metabolites Show Distinct Agonistic and Antagonistic Properties on Estrogen Receptor {alpha} (ER{alpha}) and ER{beta} in Human Cells Toxicol. Sci., July 1, 2004; 80(1): 14 - 25. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Kim, S. Cheung, and M. K. Hellerstein Isolation of nuclei from label-retaining cells and measurement of their turnover rates in rat colon Am J Physiol Cell Physiol, June 1, 2004; 286(6): C1464 - C1473. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Cabanes, M. Wang, S. Olivo, S. DeAssis, J.-A. Gustafsson, G. Khan, and L. Hilakivi-Clarke Prepubertal estradiol and genistein exposures up-regulate BRCA1 mRNA and reduce mammary tumorigenesis Carcinogenesis, May 1, 2004; 25(5): 741 - 748. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. D. Allred, K. F. Allred, Y. H. Ju, L. M. Clausen, D. R. Doerge, S. L. Schantz, D. L. Korol, M. A. Wallig, and W. G. Helferich Dietary genistein results in larger MNU-induced, estrogen-dependent mammary tumors following ovariectomy of Sprague-Dawley rats Carcinogenesis, February 1, 2004; 25(2): 211 - 218. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. G. Foster, E. V. Younglai, O. Boutross-Tadross, C. L. Hughes, and M. G. Wade Mammary Gland Morphology in Sprague-Dawley Rats following Treatment with an Organochlorine Mixture in Utero and Neonatal Genistein Toxicol. Sci., January 1, 2004; 77(1): 91 - 100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Chen, K. P. Tan, W. E. Ward, and L. U. Thompson Exposure to Flaxseed or Its Purified Lignan during Suckling Inhibits Chemically Induced Rat Mammary Tumorigenesis Experimental Biology and Medicine, September 1, 2003; 228(8): 951 - 958. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Kavanaugh and J. E. Green The Use of Genetically Altered Mice for Breast Cancer Prevention Studies J. Nutr., July 1, 2003; 133(7): 2404S - 2409. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Belenky, J. Prasain, H. Kim, and S. Barnes DING, a Genistein Target in Human Breast Cancer: A Protein Without a Gene J. Nutr., July 1, 2003; 133(7): 2497S - 2501. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Tsuda, A. Naito, C. K. Kim, K. Fukamachi, H. Nomoto, and M. A. Moore Carcinogenesis and Its Modification by Environmental Endocrine Disruptors: In Vivo Experimental and Epidemiological Findings Jpn. J. Clin. Oncol., June 1, 2003; 33(6): 259 - 270. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Kurzer Phytoestrogen Supplement Use by Women J. Nutr., June 1, 2003; 133(6): 1983S - 1986. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Yang, S. M. Edgerton, S. D. Kosanke, T. L. Mason, K. M. Alvarez, N. Liu, R. T. Chatterton, B. Liu, Q. Wang, A. Kim, et al. Hormonal and Dietary Modulation of Mammary Carcinogenesis in Mouse Mammary Tumor Virus-c-erbB-2 Transgenic Mice Cancer Res., May 15, 2003; 63(10): 2425 - 2433. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Jeruss, N. X. Liu, Y. Chung, G. Magrane, F. Waldman, S. Edgerton, X. Yang, and A. D. Thor Characterization and chromosomal instability of novel derived cell lines from a wt-erbB-2 transgenic mouse model Carcinogenesis, April 1, 2003; 24(4): 659 - 664. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Rowlands, R. Hakkak, M. J. J. Ronis, and T. M. Badger Altered Mammary Gland Differentiation and Progesterone Receptor Expression in Rats Fed Soy and Whey Proteins Toxicol. Sci., November 1, 2002; 70(1): 40 - 45. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Hilakivi-Clarke, E. Cho, A. Cabanes, S. DeAssis, S. Olivo, W. Helferich, M. E. Lippman, and R. Clarke Dietary Modulation of Pregnancy Estrogen Levels and Breast Cancer Risk among Female Rat Offspring Clin. Cancer Res., November 1, 2002; 8(11): 3601 - 3610. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Jin and R. S. MacDonald Soy Isoflavones Increase Latency of Spontaneous Mammary Tumors in Mice J. Nutr., October 1, 2002; 132(10): 3186 - 3190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Cotroneo, J. Wang, W. A. Fritz, I.-E. Eltoum, and C. A. Lamartiniere Genistein action in the prepubertal mammary gland in a chemoprevention model Carcinogenesis, September 1, 2002; 23(9): 1467 - 1474. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. Wu, P. Wan, J. Hankin, C.-C. Tseng, M. C. Yu, and M. C. Pike Adolescent and adult soy intake and risk of breast cancer in Asian-Americans Carcinogenesis, September 1, 2002; 23(9): 1491 - 1496. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. W. Jakes, S. W. Duffy, F.-C. Ng, F. Gao, E.-H. Ng, A. Seow, H.-P. Lee, and M. C. Yu Mammographic Parenchymal Patterns and Self-reported Soy Intake in Singapore Chinese Women Cancer Epidemiol. Biomarkers Prev., July 1, 2002; 11(7): 608 - 613. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R. Misra, S. D. Hursting, S. N. Perkins, N. Sathyamoorthy, J. C. Mirsalis, E. S. Riccio, and J. A. Crowell Genotoxicity and Carcinogenicity Studies of Soy Isoflavones International Journal of Toxicology, July 1, 2002; 21(4): 277 - 285. [Abstract] [PDF]
|
|
|
|
|
|
L. You, M. Sar, E. J. Bartolucci, B. S. McIntyre, and R. Sriperumbudur Modulation of Mammary Gland Development in Prepubertal Male Rats Exposed to Genistein and Methoxychlor Toxicol. Sci., April 1, 2002; 66(2): 216 - 225. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. I. Block, A. Constantinou, L. Hilakivi-Clarke, C. Hughes, D. Tripathy, J. A. Tice, K. Block, and K. Block Point-Counterpoint: Soy Intake for Breast Cancer Patients Integr Cancer Ther, March 1, 2002; 1(1): 90 - 100. [PDF]
|
|
|
|
|
|
C. A. Lamartiniere, M. S. Cotroneo, W. A. Fritz, J. Wang, R. Mentor-Marcel, and A. Elgavish Genistein Chemoprevention: Timing and Mechanisms of Action in Murine Mammary and Prostate J. Nutr., March 1, 2002; 132(3): 552S - 558. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Badger, M. J. J. Ronis, R. Hakkak, J. C. Rowlands, and S. Korourian The Health Consequences of Early Soy Consumption J. Nutr., March 1, 2002; 132(3): 559S - 565. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Maskarinec, A. E. Williams, J. S. Inouye, F. Z. Stanczyk, and A. A. Franke A Randomized Isoflavone Intervention among Premenopausal Women Cancer Epidemiol. Biomarkers Prev., February 1, 2002; 11(2): 195 - 201. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Lamartiniere, J. Wang, M. Smith-Johnson, and I.-E. Eltoum Daidzein: Bioavailability, Potential for Reproductive Toxicity, and Breast Cancer Chemoprevention in Female Rats Toxicol. Sci., February 1, 2002; 65(2): 228 - 238. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. H. Ju, C. D. Allred, K. F. Allred, K. L. Karko, D. R. Doerge, and W. G. Helferich Physiological Concentrations of Dietary Genistein Dose-Dependently Stimulate Growth of Estrogen-Dependent Human Breast Cancer (MCF-7) Tumors Implanted in Athymic Nude Mice J. Nutr., November 1, 2001; 131(11): 2957 - 2962. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Messina and C. L. Loprinzi Soy for Breast Cancer Survivors: A Critical Review of the Literature J. Nutr., November 1, 2001; 131(11): 3095S - 3108. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.-J. W. Lu, K. E. Anderson, J. J. Grady, and M. Nagamani Effects of an Isoflavone-Free Soy Diet on Ovarian Hormones in Premenopausal Women J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3045 - 3052. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. C. Lewis, S. Hudgins, A. Lewis, K. Schorr, R. Sommer, R. E. Peterson, J. A. Flaws, and P. A. Furth In Utero and Lactational Treatment with 2,3,7,8-Tetrachlorodibenzo-p-dioxin Impairs Mammary Gland Differentiation but Does Not Block the Response to Exogenous Estrogen in the Postpubertal Female Rat Toxicol. Sci., July 1, 2001; 62(1): 46 - 53. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. D. Allred, K. F. Allred, Y. H. Ju, S. M. Virant, and W. G. Helferich Soy Diets Containing Varying Amounts of Genistein Stimulate Growth of Estrogen-dependent (MCF-7) Tumors in a Dose-dependent Manner Cancer Res., July 1, 2001; 61(13): 5045 - 5050. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. O. Shu, F. Jin, Q. Dai, W. Wen, J. D. Potter, L. H. Kushi, Z. Ruan, Y.-T. Gao, and W. Zheng Soyfood Intake during Adolescence and Subsequent Risk of Breast Cancer among Chinese Women Cancer Epidemiol. Biomarkers Prev., May 1, 2001; 10(5): 483 - 488. [Abstract] [Full Text]
|
|
|
|
|
|
T. M. Badger, M. J. J. Ronis, and R. Hakkak Developmental Effects and Health Aspects of Soy Protein Isolate, Casein, and Whey in Male and Female Rats International Journal of Toxicology, May 1, 2001; 20(3): 165 - 174. [Abstract] [PDF]
|
|
|
|
|
|
L. Hilakivi-Clarke, E. Cho, S. deAssis, S. Olivo, E. Ealley, K. B. Bouker, J. N. Welch, G. Khan, R. Clarke, and A. Cabanes Maternal and Prepubertal Diet, Mammary Development and Breast Cancer Risk J. Nutr., January 1, 2001; 131(1): 154S - 157. [Full Text]
|
|
|
|
|
|
R. C. Santell, N. Kieu, and W. G. Helferich Genistein Inhibits Growth of Estrogen-Independent Human Breast Cancer Cells in Culture but Not in Athymic Mice J. Nutr., July 1, 2000; 130(7): 1665 - 1669. [Abstract] [Full Text]
|
|
|
|
|
|
C. A Lamartiniere Protection against breast cancer with genistein: a component of soy Am. J. Clinical Nutrition, June 1, 2000; 71(6): 1705S - 1707. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. E. Favoni and A. De Cupis The Role of Polypeptide Growth Factors in Human Carcinomas: New Targets for a Novel Pharmacological Approach Pharmacol. Rev., June 1, 2000; 52(2): 179 - 206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ohta, S. Nakatsugi, K. Watanabe, T. Kawamori, F. Ishikawa, M. Morotomi, S. Sugie, T. Toda, T. Sugimura, and K. Wakabayashi 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 Carcinogenesis, May 1, 2000; 21(5): 937 - 941. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. M. Brown and C. A. Lamartiniere Genistein Regulation of Transforming Growth Factor-{{alpha}}, Epidermal Growth Factor (EGF), and EGF Receptor Expression in the Rat Uterus and Vagina Cell Growth Differ., May 1, 2000; 11(5): 255 - 260. [Abstract] [Full Text]
|
|
|
|
|
|
M. J Messina Legumes and soybeans: overview of their nutritional profiles and health effects Am. J. Clinical Nutrition, September 1, 1999; 70(3): 439S - 450. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C.L. Tou and L. U. Thompson Exposure to flaxseed or its lignan component during different developmental stages influences rat mammary gland structures Carcinogenesis, September 1, 1999; 20(9): 1831 - 1835. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Hunter, L. C. Hodges, P. M. Vonier, R. Fuchs-Young, M. M. Gottardis, and C. L. Walker Estrogen Receptor Activation via Activation Function 2 Predicts Agonism of Xenoestrogens in Normal and Neoplastic Cells of the Uterine Myometrium Cancer Res., July 1, 1999; 59(13): 3090 - 3099. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. FANTI, B. P. SAWAYA, L. J. CUSTER, and A. A. FRANKE Serum Levels and Metabolic Clearance of the Isoflavones Genistein and Daidzein in Hemodialysis Patients J. Am. Soc. Nephrol., April 1, 1999; 10(4): 864 - 871. [Abstract] [Full Text]
|
|
|
|
|
|
K. D. R. Setchell and A. Cassidy Dietary Isoflavones: Biological Effects and Relevance to Human Health J. Nutr., March 1, 1999; 129(3): 758 - 758. [Abstract] [Full Text]
|
|
|
|
|
|
W. Zheng, Q. Dai, L. J. Custer, X.-O. Shu, W.-Q. Wen, F. Jin, and A. A. Franke Urinary Excretion of Isoflavonoids and the Risk of Breast Cancer Cancer Epidemiol. Biomarkers Prev., January 1, 1999; 8(1): 35 - 40. [Abstract] [Full Text]
|
|
|
|
|
|
A. L. Murkies, G. Wilcox, and S. R. Davis Phytoestrogens J. Clin. Endocrinol. Metab., February 1, 1998; 83(2): 297 - 303. [Abstract] [Full Text]
|
|