Hexachlorobenzene alters the normal cell cycle progression in MCF-7 breast cancer cell line

VENTURA CLARA; GAIDO VIRGINIA; PONTILLO CAROLINA; NÚÑEZ MARIEL; KLEIMAN DE PISAREV, DIANA; RIVERA ELENA; RANDI ANDREA; COCCA CLAUDIA

Congreso; 47th Congress of the European Societies of Toxicology EUROTOX 2011; 2011

Hexachlorobenzene (HCB) is an organochlorine pollutant highly persistent in our environment. We demonstrated that HCB induces estrogen receptor alpha (RE)-dependent cell proliferation in RE+ MCF-7 cell line. We studied if the HCB proliferation induction is associated with cell cycle modifications or with proteins involved in cell cycle regulation. MCF-7 cells were exposure to 5×10−3; 5×10−2; 5×10− and 5M HCB. Flow cytometry was performed for cell cycle studies. Western blots, inmunofluorescence and confocal microscopy were employed for protein levels and localization studies. 5×10−3 M HCB induced an increment of 100% of the cells in phase S (p < 0.001) and an increase of 200% of PCNA (p < 0.001), 10% of cyclin E (pNS) and 50% of cyclin D1 levels (p < 0.01) after 30 h of exposure. No in p27 levels were detected. However, after 1 hexposition to 5×10−3 MHCB, an increase in p27 cytosolic expressionwasobserved and itwasassociated with an increment of c-Src in membrane. Conversely, 5MHCB also induced an increase in cell number in phase S but it could not be related with changes in cyclin levels or alterations on c-Src and p27 localization.Weinstead observed that 5M HCB induced an increase in the percentage of cells in sub-G0 phase. Conclusion: 5×10−3 M HCB alters the normal cell cycle progression and c-Src and p27 could be involved in this effect. Furthermore, elevated HCB concentrations induced a delay in S-phase progression and an amplification of cells in sub-G0 phase.