Genotoxicity of cisplatin and carboplatin in cultured human lymphocytes: a comparative study

Abstract

Cisplatin and carboplatin are integral parts of many antineoplastic management regimens. Both platinum analogues are potent DNA alkylating agents that robustly induce genomic instability and promote apoptosis in tumor cells. Although the mechanism of action of both drugs is similar, cisplatin appears to be more cytotoxic. In this study, the genotoxic potential of cisplatin and carboplatin was compared using chromosomal aberrations (CAs) and sister-chromatid exchange (SCE) assays in cultured human lymphocytes. Results showed that cisplatin and carboplatin induced a significant increase in CAs and SCEs compared to the control group (p<0.01). Levels of induced CAs were similar in both drugs; however, the magnitude of SCEs induced by cisplatin was significantly higher than that induced by carboplatin (p<0.01). With respect to the mitotic and proliferative indices, both cisplatin and carboplatin significantly decreased mitotic index (p<0.01) without affecting the proliferative index (p>0.05). In conclusion, cisplatin was found to be more genotoxic than carboplatin in the SCE assay in cultured human lymphocytes, and that might explain the higher cytotoxicity of cisplatin.

Prolonged Surgical Interval Following Chemotherapy in a Patient With Idiopathic Subglottic Stenosis (iSGS): Case Report and Brief Review of Literature

“…The timing of this finding led us to investigate possible mechanisms for the observed stabilization of fibrosis following carboplatin/doxorubicin. 5,6 Although known for myelosuppression, chemotherapeutic agents are variable in their impact on immune cells and various cell populations. 7 For instance, pemetrexed, the multitargeted antifolate used in combination with carboplatin in regimen 1 for our patient, predominantly affects neutrophils.…”

“…9 Platinum-based chemotherapeutics, such as the DNA alkylating agent carboplatin, have also shown cytotoxicity against human lymphocytes in vitro. 6 One study showed that patients with mesothelioma treated with the pemetrexed/carboplatin combination had significant reduction in total lymphocytic and CD4+ count at the conclusion of each 21-day cycle. 10 Although studies support the myelosuppressive effects of pemetrexed and carboplatin, this regimen did not appear to have an impact on our patient's dilation interval as she required an endoscopic excision and dilation in the middle of the regimen and again about a year after completion.…”

Assessment of the genotoxicity and cytotoxicity of etazolate in cultured human lymphocytes

“…Cultured cells were treated with different concentrations of etazolate and the positive control (cisplatin, Sigma-Aldrich, USA; final concentration 0.4 μg/ml) in the last 24 hours of the 72hour incubation period (Azab et al, 2019). After cell incubation, harvesting was initiated by arresting the cultured cells for 2 hours in the mitotic phase with 0.1 µg/ml colcemid (Sigma-Aldrich) (Mhaidat et al, 2016).…”

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“…A volume of 0.9 ml heparinized blood was added to 9.1 mL of Peripheral Blood lymphocytes for chromosome analysis, max complete karyotyping media in order to establish lymphocyte cultures. Then, this was incubated at 37 °C temperature in a CO 2 incubator with suitable moisture content 30 .…”