A peer-reviewed open access journal published by the National Institute of Environmental Health Sciences

In this review, we examine the continually expanding and increasingly compelling data linking radiation and various chemicals in our environment to the current high incidence of breast cancer. Singly and in combination, these toxicants may have contributed significantly to the increasing rates of breast cancer observed over the past several decades. Exposures early in development from gestation through adolescence and early adulthood are particularly of concern as they re-shape the program of genetic, epigenetic and physiological processes in the developing mammary system, leading to an increased risk for developing breast cancer. In the 8 years since we last published a comprehensive review of the relevant literature, hundreds of new papers have appeared supporting this link, and in this update, the evidence on this topic is more extensive and of better quality than that previously available. Increasing evidence from epidemiological studies, as well as a better understanding of mechanisms linking toxicants with development of breast cancer, all reinforce the conclusion that exposures to these substances – many of which are found in common, everyday products and byproducts – may lead to increased risk of developing breast cancer. Moving forward, attention to methodological limitations, especially in relevant epidemiological and animal models, will need to be addressed to allow clearer and more direct connections to be evaluated.

Ovarian hormones, particularly 17 beta-estradiol, have important effects on body fat levels in rats, but it is not known whether 17 beta-estradiol can act directly on various fat depots to affect adiposity or whether these effects are entirely indirect (e.g. via food intake, exercise, or various metabolic actions). We have found high affinity, estrogen-specific macromolecular binding of 17 beta-[3H]estradiol in the cytoplasmic fraction of adipose tissues from ovariectomized rats. Saturation analysis indicates a Kd of 7.4 X 10(-10) M, and binding is inhibited by unlabeled 17 beta-estradiol or 11 beta-methoxy-17-ethynyl-1,3,5(10)-triene-3,17beta-diol (R2858) but not by progesterone, 5 alpha-dihydrotestosterone, or cortisol. 17 beta-[3H]Estradiol binding is virtually abolished by incubation with pronase but not with DNase or RNase, indicating that the binding macromolecule is probably a protein. Binding is seen in all adipose tissues studied, including abdominal, sc, and brown fat. Binding site concentration is highest in parametrial fat pads, followed by retroperitoneal, brown, omental, and inguinal depots. Binding is also seen in the cytoplasmic fraction of isolated parametrial adipocytes. These data indicate that the various adipose tissues might be estrogen target tissues in rats. Therefore, it is possible that estrogenic effects on body weight and composition could be mediated in part by direct estrogen action on adipose tissues.