Exposure to environmental pollutants may alter proangiogenic ability and promotes tumor growth. Hexachlorobenzene (HCB) is an organochlorine pesticide found in maternal milk and it is a ligand of the aryl hydrocarbon receptor (AhR). We demonstrated that H

CLARA VENTURA; ANDRÉS VENTURINO; NADIA BOURGUIGNON; MARIA ROSA RAMOS NIETO; NOELIA MIRET; ANDREA RANDI; MARIEL NÚÑEZ ; CLAUDIA COCCA

Edimburgo

Congreso; EUROTOX; 2014

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. Female Sprague Dawley rats 40 days old were exposed for 100 days to CPF 0.01 or 1 mg/Kg/day. Pituitary (LH and FSH) and steroid (estradiol, progesterone and testosterone) serum hormone levels were measured. Mammary gland and NMU-induced-mammary tumors were also analyzed. In mammary tissue, CPF (0.01 mg/Kg/day) induced expansion of the ductal network versus control (17±2vs11±1 number of ducts/field; p<0.01). CPF (0.01 and 1 mg/Kg/day) riced alveolar structures versus control (81±7 and 78±7 vs 60±6, number of alveoli/field, respectively; p<0.05). An increased number of epithelial ductal cells expressing progesterone receptor (PgR) was detected (CPF0.01:19±3; CPF1:20±3; CPF0:13±2; p<0.05). CPF 1 (mg/Kg/day) decreased estradiol (12.1±2.8vs20.8±2.1 pg/mL; p<0.05) and progesterone (2.5±0.5vs4.0±0.3 ng/mL; p<0.05) levels and slightly increased testosterone values (pNS). CPF did not affect LH and FSH values. Finally, CPF (0.01 and 1 mg/Kg/day) reduced tumor latency period (p<0.05) and in the number of tumors in rats bearing mammary cancer (p<0.05). Therefore, CPF may act as an endocrine disruptor altering estradiol and progesterone serum levels and inducing PgR expression and changes in the morphology of the mammary tissue. Tumors multiplicity increase may be caused by the augment of alveolar structures pointing that CPF could increase the susceptibility to breast cancer.