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

C VENTURA; V GAIDO; C A PONTILLO; M NUÑEZ; D KLEIMAN; E RIVERA; A RANDI; C COCCA

Paris

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

EUROTOX

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 alfa+ 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 0.005; 0.05; 0.5 and 5 Micromolar HCB. Flow cytometry was performed for cell cycle studies. Western blots, inmunofluorescence and confocal microscopy were employed for protein levels and localization studies. 0.005 Micromolar HCB induced an increment of 100% of the cells in phase S (p lower than 0.001) and an increase of 200% of PCNA (p lower than 0.001), 10% of cyclin E (pNS) and 50% of cyclin D1 levels (p lower than 0.01) after 30 h of exposure. No alterations in p27 levels were detected. However, after 1 hexposition to 0.005 Micromolar HCB, an increase in p27 cytosolic expressionwasobserved and itwasassociated with an increment of c-Src in membrane. Conversely, 5 Micromolar HCB 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 5 Micromolar HCB induced an increase in the percentage of cells in sub-G0 phase. Conclusion: 0.005 Micromolar 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.