The impact of concentration and administration time on the radiomodulating properties of undecylprodigiosin in vitro

Abstract

Undecylprodigiosin pigment (UPP) is reported to display cytotoxic activity towards various types of tumours. Nevertheless, its efficacy in modifying the cellular response to ionising radiation is still unknown. In this study, the radiomodulating effects of UPP were investigated. The effects of UPP were assessed in vitro by treating cultures of human peripheral blood with UPP and ionising radiation using two treatment regimens, the UPP pre-irradiation treatment and UPP post-irradiation treatment. The activity of UPP was investigated evaluating its effects on the radiation-induced micronuclei formation, cell proliferation, and induction of apoptosis. The redox modulating effects of UPP were examined measuring the catalase activity and the level of malondialdehyde, as a measure of oxidative stress. The results showed that UPP effects on cellular response to ionising radiation depend on its concentration and the timing of its administration. At low concentration, the UPP displayed radioprotective effects in γ-irradiated human lymphocytes while at higher concentrations, it acted as a radiosensitiser enhancing either mitotic catastrophe or apoptosis depending on the treatment regimen. The UPP modified redox processes in cells, particularly when it was employed prior to γ-irradiation. Our data highlight the importance of further research of the potential of UPP to sensitize tumour cells to radiation therapy by inhibiting pathways that lead to treatment resistance.

In vitro assessment of the cytotoxic, DNA damaging, and cytogenetic effects of hydroquinone in human peripheral blood lymphocytes

“…Although the lymphocyte model is common in genetic toxicology testing and has been recently used in studies employing similar methods as ours (13,14,17), the fact that human lymphocytes represent a population of resting cells that do not possess intrinsic metabolic activation suggests the need for further studies using other appropriate cell lines to unequivocally prove the obtained results. Lastly, we are aware that testing a much wider range of hydroquinone concentrations and using more sophisticated methods (e.g., specific modifications of the comet assay and more accurate methods for the detection of apoptosis) would provide a more accurate explanation of the observed effects, but at the moment this was not possible due to various technical and financial constraints.…”

“…The contradictory results obtained thus far using well-established cytogenetic methods call for further studies, which motivated us to perform this investigation. Its aim was to explore the mechanisms of hydroquinone toxicity and assess the relationships between its cytotoxic, genotoxic, and cytogenetic effects tested at 8, 140, and 280 µg mL -1 in human peripheral blood lymphocytes exposed for 24 h. This experimental model was chosen since lymphocytes are primary cells with a stable genome, commonly used for genotoxicity testing in many contemporary studies (13)(14)(15)(16)(17). The outcomes of treatment were evaluated using the apoptosis/necrosis assay, the alkaline comet assay, and the cytokinesis-block micronucleus (CBMN) cytome assay.…”

In vitro safety assessment of the strawberry tree (Arbutus unedo L.) water leaf extract and arbutin in human peripheral blood lymphocytes

“…Lymphocytes were chosen as a model system as they represent a common source of primary cells with a stable genome, which makes them particularly useful for genotoxicity testing, as confirmed in many contemporary studies (Aydin et al 2015;Farhan et al 2015;Turkez et al 2015;Branica et al 2016;Valencia-Quintana et al 2016a, b;Petrović et al 2017;Qari and El-Assouli 2017;Sreejaya et al 2017). They are collected in a fairly non-invasive manner and do not entail special pre-treatment.…”