DNA damage, ɣH2AX and 53-BP1 status as predictive factors of response to platinum analogues-based chemotherapy

SOTTILE FLEURY ML; REDONDO AL; GARCÍA MB; FLORES LEIVA R; IBARRA J.; VARGAS ROIG LM; NADIN SB

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Sociedades de Biociencias

Cisplatin (cisPt) constitute a widely used chemotherapeutic drug in the treatment of solid tumors. Its cytotoxic mode of action is based on the formation of DNA-interstrand and -intrastrand crosslinks with purine bases, which interfere with normal DNA function. We have reported that alkaline comet assay may constitute a useful technique to study the DNA damage and repair status and to predict response to chemotherapy in peripheral blood leukocytes (PBL) from cancer patients. γH2AX phosphorylation has been proposed as a sensitive marker of DNA double-strand breaks (DSBs). 53-BP1 is DNA damage response factor. The aim of our work was to determine DNA damage and repair rate, and to stablish their predictive value in peripheral blood leukocytes (PBL) from cancer patients treated with cisPt. We isolated PBL from 5 healthy persons and 12 cancer patients before chemotherapy. PBL were in vitro exposed to cisPt(200 μM, 1 h) or hyperthermia (42°C, 1 h), 24 h before cPt treatment(H+cisPt). The cells were harvested at: T0 (immediately after cisPt)and T24 (24 h after recovery). DNA damage/repair were evaluated by alkaline comet assay and by immunocytochemistry using specific antibodies against γH2AX and 53-BP1. At basal conditions, healthy individuals showed larger number of γH2AX (P˂0,05) and 53-BP1 foci (P