Bleomycin-induced genotoxicity in vitro in human peripheral blood lymphocytes evidenced as complex chromosome- and chromatid-type aberrations

Lal, Aswathy S.; Begum, S. Kauser; Bharadwaj, Sraddha S; Lalitha, V.; Vijayalakshmi, J.; Paul, Solomon F.D.; Ravi, Maddaly

doi:10.1016/j.tiv.2018.10.013

Cited by 6 publications

(2 citation statements)

References 16 publications

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“…In order to evaluate whether the upregulation in caveolin-1 levels is linked to DSB formation, we used bleomycin, a radiomimetic drug that also causes DSB [ 31 ]. Treatment of the same control and OA samples with bleomycin also increased caveolin-1 protein levels in the control cells, but no significant changes were observed in OA chondrocytes ( Figure 2 B,D).…”

Section: Resultsmentioning

confidence: 99%

Oxidative Stress Response Is Mediated by Overexpression and Spatiotemporal Regulation of Caveolin-1

et al. 2020

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Oxidative stress (OS) has been linked to the aetiology of many diseases including osteoarthritis (OA). Recent studies have shown that caveolin-1—a structural protein of plasma membrane’s caveolae—is upregulated in response to OS. Here, we explore the function of caveolin-1 in chondrocytes derived from healthy individuals (control) and OA patients that were subjected to exogenous OS. We showed that caveolin-1 was upregulated in response to acute OS in the control, but not in OA chondrocytes. Moreover, OS-induced DNA damage analysis revealed that control cells started repairing the DNA lesions 6 h post-oxidative treatment, while OA cells seemed unable to restore these damages. Importantly, in the control cells, we observed a translocation of caveolin-1 from the membrane/cytoplasm in and out of the nucleus, which coincided with the appearance and restoration of DNA lesions. When caveolin-1 was prevented from translocating to the nucleus, the control cells were unable to repair DNA damage. In OA cells, no such translocation of caveolin-1 was observed, which could account for their inability to repair DNA damage. Taken together, these results provide novel insights considering the role of caveolin-1 in response to OS-induced DNA damage while revealing its implication in the pathophysiology of OA.

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Section: Resultsmentioning

confidence: 99%

Oxidative Stress Response Is Mediated by Overexpression and Spatiotemporal Regulation of Caveolin-1

et al. 2020

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“…Caution: BLM is cytotoxic, genotoxic, teratogenic, and mutagenic and should be handled with care [22,23].…”

Section: Experimental/materials and Methodsmentioning

confidence: 99%

An effective validation of analytical method for determination of a polar complexing agent: the illustrative case of cytotoxic bleomycin

et al. 2023

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The effectiveness of highly polar agents in cancer treatment is well recognized, but their physicochemical properties make their analytical determination a demanding task. Their analysis requires peculiar sample preparation and chromatographic separation, which heavily impacts the precision of such an analytical method. As a case study, we chose a polar cytotoxic bleomycin, which is a mixture of complexing congeners with relatively high molecular mass, a fact that creates an added challenge in regard to its detection via electrospray mass spectrometry. These issues combined lead to a deprived method performance, so the aim of this study is manifold, i.e., to optimize, validate, and establish quality performance measures for determination of bleomycin in pharmaceutical and biological specimens. Quantification of bleomycin is done at diametrically different concentration levels: at the concentrations relevant for analysis of pharmaceutical dosage forms it is based on a direct reversed-phase HPLC-UV detection, involving minimum sample pretreatment. On the contrary, analysis of bleomycin in biological specimens requires phospholipid removal and protein precipitation followed by HILIC chromatography with MS/MS detection of bleomycin A2 and B2 copper complexes being the predominant species. This study further attempts to solve the traceability issue in the absence of certified reference standards, determines measurement uncertainty, investigates BLM stability and method performance characteristics, and, last but not least, provides an explanatory example of how a method quality assurance procedure should be established in case of an exceedingly complex analytical method. Graphical abstract

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Chromosomal Aberration Test in Human Lymphocytes

Johannes¹,

Obe²

2019

Methods in Molecular Biology

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Bleomycin-induced genotoxicity in vitro in human peripheral blood lymphocytes evidenced as complex chromosome- and chromatid-type aberrations

Cited by 6 publications

References 16 publications

Oxidative Stress Response Is Mediated by Overexpression and Spatiotemporal Regulation of Caveolin-1

Oxidative Stress Response Is Mediated by Overexpression and Spatiotemporal Regulation of Caveolin-1

An effective validation of analytical method for determination of a polar complexing agent: the illustrative case of cytotoxic bleomycin

Chromosomal Aberration Test in Human Lymphocytes

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