Role of the organophosphate chlorpyrifos as an endocrine disruptor in mammary gland.

C VENTURA; MR RAMOS NIETO; A VENTURINO; N BOURGUIGNON; N MIRET; A RANDI; M NUÑEZ; C COCCA

Edimburgo

Congreso; 50th Congress of the European Societies of Toxicology. EUROTOX; 2014

European Societies of Toxicology

Resumen aceptado: Many of the chemicals found to be endocrine disruptors display controversy about whether low environmental doses produce harmful effects in humans. We demonstrated that the pesticide chlorpyrifos (CPF) may act as endocrine disruptor in vitro since induces estrogen receptor phosphorylation. Here, we studied the effect of CPF as an endocrine disruptor in vivo. For that female Sprague Dawley rats 40 days old were exposed to CPF 0.01 or 1 mg/Kg/day. The pituitary (LH and FSH) and steroid (estradiol, progesterone and testosterone) serum hormone levels were measured. Mammary gland and breast tumors were also analyzed. In mammary tissue, CPF (0.01 and 1 mg/Kg/day) induced expansion of the ductal network with a significant increase in ducts (p lower than 0.01) and alveolar structures relative to the control (p lower than 0.05). Moreover, an increased number of epithelial ductal cells expressing progesterone receptor (PgR) was detected (p lower than 0.05). CPF 1 (mg/Kg/day) decreased estradiol (p lower than 0.05) and progesterone (p lower than 0.05) levels and slightly increased testosterone values (pNS). CPF did not affect LH and FSH values. Finally, we observed an decreased in tumors latency period (p lower than 0.05) and in the number of tumors in rats bearing mammary cancer (p lower than 0.05). We conclude that CPF may act as an endocrine disruptor increasing PgR expression in the mammary tissue associated to the morphology changes induced in the gland. The increment in tumors multiplicity may be caused by the augment of alveolar structures. The diminished estradiol levels which could be due to changes in stoideogenesis. Therefore, CPF may act as endocrine disruptor and increase the susceptibility to breast cancer.