Genistein studies in rats: potential for breast cancer prevention and reproductive and developmental toxicity

被引:101
作者
Lamartiniere, CA [1 ]
Zhang, JX [1 ]
Cotroneo, MS [1 ]
机构
[1] Univ Alabama Birmingham, Dept Pharmacol & Toxicol, Birmingham, AL 35294 USA
关键词
soy; genistein; mammary cancer prevention; reproduction; development; toxicology;
D O I
10.1093/ajcn/68.6.1400S
中图分类号
R15 [营养卫生、食品卫生]; TS201 [基础科学];
学科分类号
100403 ;
摘要
Asian women and men who consume traditional diet high in soy products have low incidences of breast and prostate cancers, respectively. Yet Asians who immigrate to the United States and adopt a Western diet lose this protection. We investigated the potential of genistein, a component of soy, to protect against breast cancer and to cause reproductive and developmental toxicity. Our study showed that injections of genistein in rats during the prepubertal period resulted in a 50% reduction of chemically induced mammary tumorigenesis. Studies in mammary whole mounts revealed that prepubertal genistein exposure resulted in fewer terminal end buds and more lobules type LI. Cell proliferation in the terminal end buds of adult rats treated prepubertally with genistein was less than that in animals treated with the vehicle (dimethyl sulfoxide). Reproductive and developmental toxicity studies did not find significant alterations to fertility, number of male and female offspring, body weight, anogenital distance, vaginal opening, testes descent, estrus cycle, or follicular development. We concluded that pharmacologic doses of genistein given to immature rats enhance mammary gland differentiation, resulting in a significantly less proliferative gland that is not as susceptible to mammary cancer. We speculate that breast cancer protection in Asian women consuming traditional soy-containing diets is, in part, derived from early exposure to genistein-containing soy. We believe that early programming events are essential for cancer protection benefits.
引用
收藏
页码:1400S / 1405S
页数:6
相关论文
共 41 条
[1]   PLASMA-CONCENTRATIONS OF PHYTO-ESTROGENS IN JAPANESE MEN [J].
ADLERCREUTZ, H ;
MARKKANEN, H ;
WATANABE, S .
LANCET, 1993, 342 (8881) :1209-1210
[2]  
AKIYAMA T, 1987, J BIOL CHEM, V262, P5592
[3]  
CONSTANTINOU A, 1995, P SOC EXP BIOL MED, V208, P109
[4]  
CONSTANTINOU A, 1990, CANCER RES, V50, P2618
[5]  
Dalu A, 1998, AM J CLIN NUTR, V68, p1524S
[6]   EFFECTS OF THE TYROSINE-KINASE INHIBITOR GENISTEIN ON DNA-SYNTHESIS AND PHOSPHOLIPID-DERIVED 2ND MESSENGER GENERATION IN MOUSE 10T1/2 FIBROBLASTS AND RAT-LIVER T51B CELLS [J].
DEAN, NM ;
KANEMITSU, M ;
BOYNTON, AL .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1989, 165 (02) :795-801
[7]   GENISTEIN, A DIETARY-DERIVED INHIBITOR OF INVITRO ANGIOGENESIS [J].
FOTSIS, T ;
PEPPER, M ;
ADLERCREUTZ, H ;
FLEISCHMANN, G ;
HASE, T ;
MONTESANO, R ;
SCHWEIGERER, L .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (07) :2690-2694
[8]   EVIDENCE FOR A MORPHOLOGICAL SEX DIFFERENCE WITHIN MEDIAL PREOPTIC AREA OF RAT-BRAIN [J].
GORSKI, RA ;
GORDON, JH ;
SHRYNE, JE ;
SOUTHAM, AM .
BRAIN RESEARCH, 1978, 148 (02) :333-346
[9]  
GRUBBS CJ, 1985, J NATL CANCER I, V74, P927
[10]  
GYORGY P, 1964, NATURE, V203, P872