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

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

París

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

Sociedades Europeas de Toxicología

Hexachlorobenzene (HCB) is an organochlorine pollutant highly persistent in our environment. We have previously demonstrated that HCB induces estrogen receptor alpha (REα)-dependent cell proliferation in (REα) positive MCF-7 cell line. Our aim was to study if the proliferation induction could be associated with modifications on the normal cell cycle or on the proteins involved in cell cycle regulation. MCF-7 cells were exposure to 5.10 -3; 5.10 -2; 5.10 -1 and 5 µM HCB. 5.10 -3 µM HCB induced an increment of 100% of the cells in phase S (p<0.001). It was accompanied by an increase of 200% of PCNA (p<0.001), 10% of cyclin E (pNS) and 50% of cyclin D1 levels (p<0.01) as western blot analysis showed after 30 h of exposure. No alterations in p27 levels were detected. However, after one hour exposition to 5.10 -3 µM HCB, an increase in p27 cytosolic expression was observed and it was associated with an increment of c-Src in plasmatic membrane detected by confocal microscopy analysis. Conversely, 5 µM HCB also induced an increase in cell number in phase S but it couldn´t be related with changes in cyclin levels or alterations on c-Src and p27 localization. We have instead observed by flow cytometry that 5 µM HCB induced an increase in the percentage of cells in sub-G0 phase. Conclusion: 5.10 -3 µM 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.