RESUMO
BACKGROUND: The high morbidity and mortality of breast cancer among women is a serious problem. The adverse effects of the consumption of beef with zeranol (Z, a growth promoter widely used in beef industry in North American) residue on human health are still unknown. MATERIALS AND METHODS: The effects of Z implantation on the growth of heifer pre-adipocytes were evaluated. The stimulatory effects of Z and estradiol-17beta (E(2)) on the proliferation of pre-adipocytes isolated from control heifers and Z-implanted heifers were measured. Real-time PCR and Western-blotting analysis were performed to evaluate the expression of cyclin D1 and p53 at both mRNA and protein levels. RESULTS: The growth of pre-adipocytes from heifers bearing for 2 months of Z-implants was about 12-fold faster than that observed in control heifers. The pre-adipocytes isolated from Z-implanted heifers were more sensitive to treatment with Z and E(2). Z up-regulated the expression of cyclin D1 and down-regulated p53 in pre-adipocytes isolated from Z-implanted heifers. CONCLUSION: The implantation of Z increases body weight gain by enhancing growth of pre-adipocytes. The stimulation of pre-adipocytes division by Z and E(2) might be partially mediated by up-regulation of cyclin D1 and down-regulation of p53 at mRNA and protein levels.