Dimethyl-Benz(a)anthracene: A mammary carcinogen and a neuroendocrine disruptor

Abstract

Polycyclic Aromatic Hydrocarbons (PAHs) are potent carcinogens. Among these, dimethylbenz(a)anthracene (DMBA) is well known for its capacity to induce mammary carcinomas in female Sprague-Dawley (SD) rats. Ovariectomy suppresses the susceptibility of this model to DMBA, thus suggesting that the inducible action of the carcinogen depends on ovarian hormones. The promotion of DMBA-induced adenocarcinoma is accompanied by a series of neuroendocrine disruptions of both Hypothalamo-Pituitary-Gonadal (HPG) and Hypothalamo-Pituitary-Adrenal (HPA) axes and of the secretion of melatonin during the latency period of 2 months that precedes the occurrence of the first mammary tumor. The present review analyses the various neuroendocrine disruptions that occur along the HPG and the HPA axes, and the marked inhibitory effect of the carcinogen on melatonin secretion. The possible relationships between the neuroendocrine disruptions, which essentially consist in an increased pre-ovulatory secretion of 17β-estradiol and prolactin, associated with a marked reduction of melatonin secretion, and the decrease in gene expression of the receptors for aryl-hydrocarbons receptor (AhR) and 17β-estradiol (ERα; ERβ) are also discussed.