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  1. Chandirasekar R, Kumar BL, Sasikala K, Jayakumar R, Suresh K, Venkatesan R, et al.
    PMID: 24769293 DOI: 10.1016/j.mrgentox.2014.04.007
    Inexpensive forms of tobacco are widely used in developing countries such as India. We have evaluated genotoxicity endpoints (chromosome aberrations, micronucleus frequency, comet assay) and polymorphisms of the XRCC1 and p53 genes among smokers and smokeless tobacco (SLT) users in rural Tamilnadu, South India. Cytogenetic, DNA damage and SNP analyses were performed on peripheral blood samples; micronucleus frequency was measured in peripheral blood and buccal mucosa exfoliated cells. Both categories of tobacco users had elevated levels of genotoxic damage. SNP analysis of tobacco users revealed that 17% carry the XRCC1 gln399gln genotype and 19% carry the p53 pro72pro genotype. Both genotypes are associated with increased risk of cancer.
  2. Ooi TC, Nordin FJ, Rahmat NS, Abdul Halim SN', Sarip R, Chan KM, et al.
    PMID: 36868695 DOI: 10.1016/j.mrgentox.2022.503581
    Complexes of coinage metals can potentially be used as alternatives to platinum-based chemotherapeutic drugs. Silver is a coinage metal that can potentially improve the spectrum of efficacy in various cancers treatment, such as malignant melanoma. Melanoma is the most aggressive form of skin cancer that is often diagnosed in young and middle-aged adults. Silver has high reactivity with skin proteins and can be developed as a malignant melanoma treatment modality. Therefore, this study aims to identify the anti-proliferative and genotoxic effects of silver(I) complexes with mixed-ligands of thiosemicarbazones and diphenyl(p-tolyl)phosphine ligands in the human melanoma SK-MEL-28 cell line. The anti-proliferative effects of a series of silver(I) complex compounds labelled as OHBT, DOHBT, BrOHBT, OHMBT, and BrOHMBT were evaluated on SK-MEL-28 cells by using the Sulforhodamine B assay. Then, DNA damage analysis was performed in a time-dependent manner (30 min, 1 h and 4 h) by using alkaline comet assay to investigate the genotoxicity of OHBT and BrOHMBT at their respective IC50 values. The mode of cell death was studied using Annexin V-FITC/PI flow cytometry assay. Our current findings demonstrated that all silver(I) complex compounds showed good anti-proliferative activity. The IC50 values of OHBT, DOHBT, BrOHBT, OHMBT, and BrOHMBT were 2.38 ± 0.3 μM, 2.70 ± 0.17 μM, 1.34 ± 0.22 μM, 2.82 ± 0.45 μM, and 0.64 ± 0.04 μM respectively. Then, DNA damage analysis showed that OHBT and BrOHMBT could induce DNA strand breaks in a time-dependent manner, with OHBT being more prominent than BrOHMBT. This effect was accompanied by apoptosis induction in SK-MEL-28, as evaluated using Annexin V-FITC/PI assay. In conclusion, silver(I) complexes with mixed-ligands of thiosemicarbazones and diphenyl(p-tolyl)phosphine exerted anti-proliferative activities by inhibiting cancer cell growth, inducing significant DNA damage and ultimately resulting in apoptosis.
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