Evaluation of apoptosis induced by exposure to antineoplastic drugs in peripheral blood lymphocytes of nurses.

Abstract

Cytostatic antineoplastic drugs are considered carcinogenic and mutagenic risk factors for health workers who are occupationally exposed to them; however, the molecular mechanisms underlying these effects remain to be elucidated. Therefore, the present study aimed to investigate the underlying mechanisms of antineoplastic drugs-induced apoptosis of peripheral blood lymphocytes (PBLs) obtained from oncology nurses handling antineoplastic drugs. A microRNA (miRNA/miR) polymerase chain reaction (PCR) array was performed to analyze the expression levels of miRNAs in the PBLs from 3 trained nurses occupationally exposed to antineoplastic drugs. The effects of miR-34a on cell proliferation and apoptosis in temozolomide (TMZ) treated PBLs were analyzed by cell counting kit-8 and flow cytometry assays. The protein expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein, caspase-3 and caspase-9 were determined by western blot analysis, and miR-34a expression levels were detected using quantitative reverse transcription-PCR. The results of the present study demonstrated that miR-34a was significantly upregulated in oncology nurses that were occupationally exposed to antineoplastic drugs. In addition, TMZ suppressed cell proliferation and induced apoptosis, by promoting the expression of miR-34a, in a dose-dependent manner, and also inhibited the expression of Bcl-2. Furthermore, knockdown of miR-34a was able to reverse the reduction of cell proliferation and promotion of apoptosis induced by TMZ in PBLs. Together, these results indicated that abnormal expression of miR-34a may be considered a diagnostic marker in nurses occupationally exposed to antineoplastic drugs.