Phrakonkham P, Brouland J P, Saad H El Sheikh, Bergès R, Pimpie C, Pocard M, Canivenc-Lavier M C, Perrot-Applanat M
INRA UMR1324, Centre des Sciences du Gout et de l'Alimentation, F-21000 Dijon, France; Université de Bourgogne, Dijon, France.
INSERM U965, Hôpital Lariboisière, F-75475 Paris, France; Université Paris 7, F-75475 Paris, France; Service d'Anatomopathologie, Hôpital Lariboisière, F-75475 Paris, France.
Reprod Toxicol. 2015 Jul;54:101-9. doi: 10.1016/j.reprotox.2014.05.016. Epub 2014 Jun 8.
Endocrine disruptors may play substantial roles in the high incidence of breast cancer. We previously described how early exposure to the mixture of phytoestrogen genistein (G) and the anti-androgen vinclozolin (V) affects peripubertal mammary development. This study evaluates the carcinogenic potential of exposure to V alone or associated with G from conception until weaning in Wistar rats. Dams were exposed to V, G or GV during pregnancy/lactation. At PND50 offspring were treated with DMBA[7,12-dimethylbenz(a)anthracene]. V or GV maternal exposure decreased number of DMBA-induced mammary tumors in the offspring, without significant modifications in tumor incidence, multiplicity and latency. G exposure decreased number of tumors, incidence and multiplicity. Unexpectedly, GV exposure increased tumor volume (p=0.04 vs controls) and epithelial proliferation (p=0.001 vs controls; p=0.005 vs G,V only). All tumors were in situ carcinomas. Concluding, maternal gestation/lactation exposure to a vinclozolin and genistein mixture significantly increases offspring tumor growth without changes in carcinogenesis susceptibility.
内分泌干扰物可能在乳腺癌的高发病率中起重要作用。我们之前描述了早期接触植物雌激素染料木黄酮（G）和抗雄激素乙烯菌核利（V）的混合物如何影响青春期前乳腺发育。本研究评估了从受孕到断奶期间单独接触V或与G联合接触对Wistar大鼠的致癌潜力。在怀孕/哺乳期间，将母鼠暴露于V、G或GV。在出生后第50天（PND50），对后代用7,12-二甲基苯并(a)蒽（DMBA）进行处理。母体暴露于V或GV可减少后代中DMBA诱导的乳腺肿瘤数量，而肿瘤发生率、多发性和潜伏期无显著改变。暴露于G可减少肿瘤数量、发生率和多发性。出乎意料的是，暴露于GV会增加肿瘤体积（与对照组相比，p = 0.04）和上皮细胞增殖（与对照组相比，p = 0.001；与仅暴露于G、V相比，p = 0.005）。所有肿瘤均为原位癌。总之，母体在妊娠/哺乳期暴露于乙烯菌核利和染料木黄酮的混合物会显著增加后代肿瘤生长，而致癌易感性无变化。
