CATEGORY*: Endocrine disruptor
USED IN: Meat
Zearalenone and its synthetic derivative zeranol (Ralgro) are estrogenic compounds to which cattle and swine in the U.S. meat industry are extensively exposed.
Natural sources of zearalenone come from contamination of feed sources, including corn silage and hay, by the fungus Fusarium, which is an active producer of the chemical (Benzoni, 2008; Mirocha, 1979). Contamination of food by zearalenone and its natural metabolites (breakdown products) has been associated with the development of precocious puberty—a known risk factor for breast cancer—in young girls (Massart, 2008). These compounds have also been shown to enhance proliferation of ER+ human breast tumor cells in vitro through estrogen-mediated pathways and activation of gene profiles similar to those activated by the natural hormone estradiol (Khosrokhavar, 2009; Parveen, 2009).
The synthetic compound zeranol is a potent nonsteroidal growth promoter that mimics many of the effects of estradiol. Zeranol is used extensively in the United States and Canada to promote rapid and more efficient growth rates in animals used as sources of meat (Al-Dobaib, 2009).
Like the natural compound zearalenone, zeranol is a powerful estrogenic chemical, as demonstrated by its ability to stimulate growth and proliferation of human breast tumor cells in vitro at potencies similar to those of the natural hormone estradiol and the known carcinogen diethylstilbestrol (DES) (Leffers, 2001). Adding zeranol to cultured (in vitro) breast epithelial cells led to enhanced cell proliferation, accompanied by stimulation of the activity of protein disulfide isomerase, an enzyme whose activity is often increased in cancerous tissues (Updike, 2005).
Treatment of young adult female mice with zeranol led to increased growth and branching of mammary glands, similar to what is found in mice treated with estradiol (Sheffield, 1985). Increased ductile proliferation, in the absence of full maturation of the ducts through pregnancy and lactation, is associated with an increased risk for mammary (breast) tumors.
Brief (four-day) pre-pubertal exposure of mice or rats to either zearalenone or zeranol accelerated the onset of puberty but did not affect development of the mammary gland structures through early adulthood (Nikaido, 2005; Yuri, 2004).
A series of studies examined estrogenic activity in normal breast epithelial cells and breast cancer cells treated with zeranol. Abnormal cell growth was significant even at zeranol levels almost 30 times lower than the FDA-established limit in beef (Liu, 2002). Follow-up work demonstrated that zeranol is comparable to natural estrogen (estradiol) and the synthetic estrogen diethylstilbestrol (DES) in its ability to transform MCF-10A human breast epithelial cells to a pre-cancerous profile in vitro (Liu, 2004). Preliminary data indicate that serum from zeranol-treated beef cattle can stimulate the proliferation of normal breast epithelial cells and the transformation of breast tumor cells in vitro (Xu, 2009; Ye, 2009b).
*For chemicals that have been shown to be carcinogens, we provide classifications from two authoritative bodies: the International Agency for Research on Cancer (IARC, an international body) and the National Toxicology Program (NTP, a division of the U.S. Department of Health and Human Services). We have categorized endocrine-disrupting compounds where the body of peer-reviewed research indicates a strong foundation for doing so.