IN VITRO EVALUATION OF CYTOGENETIC DAMAGE BY GRAPHENE OXIDE (15-20 SHEETS) NANOMATERIALS IN HUMAN BLOOD LEUKOCYTES FROM HEALTHY INDIVIDUALS AND PULMONARY DISEASE PATIENTS DIAGNOSED WITH ASTHMA, COPD AND LUNG CANCER

For the past few decades, the use of graphene oxide (GO) nanomaterials (NMs) has increased exceedingly due totheir biomedical applications in the drug delivery of anti-cancer drugs. Their unique physicochemical propertiesand good surface chemistry with unbound surface functional groups enable covalent bonding with organicmolecules such as RNA and DNA, making GO NMs excellent candidates for drug delivery nanocarriers. Despitethe increased use in biomedical applications, there are concerns about their genotoxicity. Only a few studies onGO NMs’ impact on DNA have been published on humans, let alone on patients diagnosed with chronicpulmonary diseases. This study investigates for the first time the effects of commercial GO (15-20 sheets; 4-10%edge-oxidized; 1 mg/ml) in vitro, in particular the DNA damage but also other genotoxic endpoints in whole bloodand peripheral blood leucocytes (PBL) from healthy individuals and patients diagnosed with chronic pulmonarydiseases, i.e., asthma, chronic obstructive pulmonary disease (COPD), and lung cancer. After detailedcharacterization of commercial GO NMs, cytotoxicity studies were conducted using the dimethyl thiazolyldiphenyltetrazolium bromide (MTT) and neutral red uptake (NRU) assays. In contrast, genotoxicity (DNAdamage and chromosome aberration parameters) was studied using alkaline Comet and cytokinesis-blockedmicronucleus (CBMN) assays. Our results showed concentration-dependent increases in cytotoxicity,genotoxicity, and chromosome aberrations, with PBL from COPD and lung cancer patients being more sensitiveto DNA damage compared with asthma patients and healthy control individuals. GO NMs may have promisingroles in drug delivery applications when formulated to deliver drug payloads to cells for treating COPD or cancercells. But the fact that cytotoxicity, genotoxicity, and chromosome instability parameters as biomarkers of cancerrisk were increased in exposed cells from healthy individuals should be of concern regarding public health,especially in occupational exposures and in medical treatments when using GO NMs as drug delivery nanocarriers.