HSP27 AND HSP70 IN PEDIATRIC CANCER PATIENTS: RELATIONSHIP WITH DNA REPAIR.

SILVINA B. NADIN; LAURA M. VARGAS-ROIG; GISELA DRAGO; CIOCCA DR

Quebec

Congreso; First International Congress on Stress Responses in Biology and Medicine; 2003

International Cell Stress Society

Doxorubicin is widely used in chemotherapy to treat solid tumors. In previous studies, using peripheral blood lymphocytes (PBL) from healthy donors, we observed a nuclear translocation of Hsp27 and Hsp70 associated with a high DNA repair capacity (DRC) after doxorubicin and heat shock treatments. In the present study, we isolated PBL from 9 pediatric cancer patients before chemotherapy. Each sample was divided in 4 groups: group 1, control (without treatment); group 2, heat shock (heat shocked at 42°C); group 3, doxorubicin (21nM of doxorubicin); and group 4, heat shock + doxorubicin (doxorubicin administered 24 hours after heat shock). The cells were harvested at: T0 (immediately after doxorubicin) and T24 (after 24 hours of recovery). Immunocytochemistry was used to detect Hsp27 and 70, and the alkaline comet assay was used to measured DNA damage/repair. Cancer patients showed significant higher basal levels of Hsp27 and Hsp70 than controls, with a significant nuclear translocation of both Hsps, and increased percentage of damaged cells. In addition, cancer patients showed higher nuclear translocation of Hsp27 and 70 than in controls (Group 4), with a significant decreased in DRC, lower levels of hMLH1 and hMSH2 and an elevated number of damaged cells. Cancer patients did not present differences in their DRC between groups 3 and 4, this was in contrast to control healthy patients. All cancer patients are at present in complete remission.