Uterine adenocarcinoma in mice treated neonatally with genistein.
The developing fetus is uniquely sensitive to perturbation with estrogenic chemicals. The carcinogenic effect of prenatal exposure to diethylstilbestrol (DES) is the classic example. Because phytoestrogen use in nutritional and pharmaceutical applications for infants and children is increasing, we investigated the carcinogenic potential of genistein, a naturally occurring plant estrogen in soy, in an experimental animal model previously reported to result in a high incidence of uterine adenocarcinoma after neonatal DES exposure. Outbred female CD-1 mice were treated on days 1-5 with equivalent estrogenic doses of DES (0.001 mg/kg/day) or genistein (50 mg/kg/day). At 18 months, the incidence of uterine adenocarcinoma was 35% for genistein and 31% for DES. These data suggest that genistein is carcinogenic if exposure occurs during critical periods of differentiation. Thus, the use of soy-based infant formulas in the absence of medical necessity and the marketing of soy products designed to appeal to children should be closely examined.
Newbold
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RR
Developmental Endocrinology Section, Laboratory of Toxicology, Environmental Toxicology Program, Division of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. newbold1@niehs.nih.gov
Banks
E P
EP
Bullock
B
B
Jefferson
W N
WN
D000230:Adenocarcinoma / Q000139:chemically induced*; D000818:Animals; D004054:Diethylstilbestrol / Q000633:toxicity; D004968:Estrogens, Non-Steroidal / Q000633:toxicity; D005187:Fallopian Tubes / Q000002:abnormalities / Q000187:drug effects; D005260:Female; D019833:Genistein / Q000633:toxicity*; D007529:Isoflavones; D008297:Male; D051379:Mice; D048789:Phytoestrogens; D028321:Plant Preparations; D011247:Pregnancy; D014594:Uterine Neoplasms / Q000139:chemically induced*; D014599:Uterus / Q000002:abnormalities / Q000187:drug effects
D004968:Estrogens, Non-Steroidal; D007529:Isoflavones; D048789:Phytoestrogens; D028321:Plant Preparations; D004054:Diethylstilbestrol; D019833:Genistein