RESUMO
A mitogenic agent in corncob bedding and fresh corn products disrupts sexual behavior and estrous cyclicity in rats. The mitogenic activity resides in an isomeric mixture of linoleic acid derivatives with a tetrahydrofuran ring and two hydroxyl groups (THF-diols) that include 9, (12)-oxy-10,13-dihydroxystearic acid and 10, (13)-oxy-9,12-dihydroxystearic acid. Synthetic THF-diols stimulated breast cancer cell proliferation in vitro and disrupted the estrous cycle in female rats at oral doses of approximately 0.30 mg/kg body weight/day. Exposure to THF-diols may disrupt endocrine function in experimental animals at doses approximately 200 times lower than classical phytoestrogens, promote proliferation of breast or prostate cancer, and adversely affect human health.
Assuntos
Mitógenos/farmacologia , Ácidos Esteáricos/farmacologia , Zea mays/química , Animais , Ligação Competitiva , Neoplasias da Mama/patologia , Divisão Celular/efeitos dos fármacos , Sistema Endócrino/efeitos dos fármacos , Estradiol/metabolismo , Ciclo Estral/efeitos dos fármacos , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Mitógenos/química , Mitógenos/isolamento & purificação , Ratos , Ácidos Esteáricos/síntese química , Ácidos Esteáricos/química , Células Tumorais CultivadasRESUMO
Housing adult rats on ground corncob bedding impedes male and female mating behavior and causes acyclicity in females. The suppressive effects on ovarian cyclicity are mimicked by a mitogenic agent purified from the ground corncob bedding material (corn mitogen; CM), which stimulates the proliferation of estrogen receptor (ER)-positive (MCF-7 cells) and ER-negative (MDA-MD-231 cells) breast cancer cells. Purified CM does not compete for [(3)H]estradiol binding to ER or nuclear type II sites, and its effects on MCF-7 breast cancer cell proliferation are not blocked by the antiestrogen ICI-182,780. These results suggest that the active component is unlikely to be a phytoestrogen, bioflavonoid, mycotoxin, or other known endocrine-disrupting agent that modifies cell growth via ER or type II [(3)H]estradiol binding sites. CM also stimulates the proliferation of PC-3 human prostatic cancer cells in vitro, and the growth rate of PC-3 cell xenografts is accelerated in nude male mice housed on ground corncob as opposed to pure cellulose bedding. Consequently, this endocrine-disrupting agent in ground corncob bedding may influence behavioral and physiologic reproductive response profiles and malignant cell proliferation in experimental animals. Fresh corn (kernels and cob) or corn tortillas also contain CM, indicating that human exposure is likely; consequently, CM and/or related mitogens in corn products may influence human health and development.
Assuntos
Neoplasias da Mama/patologia , Mitógenos/farmacologia , Neoplasias da Próstata/patologia , Receptores de Estrogênio/efeitos dos fármacos , Zea mays/química , Animais , Divisão Celular , Sistema Endócrino/efeitos dos fármacos , Estro , Feminino , Contaminação de Alimentos , Abrigo para Animais , Humanos , Masculino , Camundongos , Camundongos Nus , Ratos , Ratos Sprague-Dawley , Receptores de Estrogênio/fisiologia , Reprodutibilidade dos Testes , Comportamento Sexual Animal/efeitos dos fármacos , Células Tumorais Cultivadas , Útero/citologiaRESUMO
The incidence of primary renal neoplasia in animals is quite low. Carcinomas are the most common primary renal tumors of dogs, cattle, and sheep. Among rabbit tumors, only uterine adenocarcinomas occur more frequently than do embryonal nephromas. However, spontaneous renal cell carcinomas in laboratory rabbits have only been reported once previously. We here report a second occurrence of a renal cell carcinoma in the laboratory rabbit.