Neoplasia as development gone awry: the role of endocrine disruptors

The hypothesis that prenatal exposure to endocrine disruptors might cause cancer arose from challenging two well-accepted notions: (i) mammalian development is merely the unfolding of a genetic programme and (ii) only mutagenic agents can cause cancer. This hypothesis required challenging genetic determinism. The ecological developmental biology (eco-devo) movement revitalized the concept of developmental plasticity through the occurrence of polyphenisms (a single genotype produces diverse phenotypes which are determined by environmental cues). Based on the principles of eco-devo and the tissue organization field theory of carcinogenesis and neoplasia, we tested the hypothesis that exposure to xenoestrogens during foetal development in rats increased the propensity to develop mammary cancer during adulthood. We chose exposure to bisphenol A (BPA) as a model for environmental oestrogen exposure. This endocrine disruptor induced the development of ductal hyperplasias and carcinoma in situ. These highly proliferative lesions contained an increased number of oestrogen receptor alpha-positive cells. Thus, foetal BPA exposure was sufficient to induce the development of oestrogen-sensitive pre-neoplastic and neoplastic lesions in the mammary gland in the absence of any additional treatment aimed at increasing tumour incidence.