In Vitro and In Vivo Genotoxicity Analysis of Gold Nanoparticles

Gold nanoparticles have been well recognized for biomedical applications, especially cancer therapeutics. As a preliminary step, it is necessary to investigate the genotoxicity of gold nanoparticles under in vitro and in vivo conditions. In vitro, chromosomal aberration study results showed that gold nanoparticles of 5 mg/ml concentration did not increase the percentage of chromosomal aberration in human peripheral blood lymphocyte cells compared to the negative control. Gold nanoparticles were evaluated erythrocyte micronucleus formation by in vivo micronucleus assay, and results showed no apparent micronucleus formation in mice after 42h exposure of gold nanoparticles. Gold nanoparticles of 600 mg/kg (body weight) were non-clastogenic in swiss albino mice.

Pembentukan Mikronukleus di Mukosa Bukal akibat Paparan Senyawa Kimia pada Berbagai Macam Pekerjaan

In general, an occupation could have hazzard and risk of exposure to genotoxic chemical compounds. These compounds could lead to micronucleus formation on buccal mucosa. This study was aimed to obtain the impact of chemical exposure on micronucleus formation in buccal mucosa at various occupations. This was a literature review study using databases of PubMed, ScienceDirect, and Google Scholar based on the keywords. The criteria of literatures were articles published in 2016-2021 using Indonesian or English language. The results showed that group compounds of polycyclic aromatic hydrocarbons (PAH), metals, carbamate, and organophospate, also compunds of silica, bezene, toluene, xylene (BTX), sevoflurane, desflurane, isoflurane, nitrous oxide, gemcitabin, and 5-fluoro uracil were genotoxic chemical compunds and could cause micronucleus formation in buccal mucosa of mechanics, grillers, miners, e-waste recyclers, construction workers, road markers, car painters, gasoline station workers, farmers, and healthcare workers. Genotoxic chemical compounds could be found excessively in occupational environment. These compounds could damage cells’ DNA and caused micronucleus formation on buccal mucosa of workers. It is suggested to study further about cell damage biomarkers caused by genotoxic chemical compound exposure.Keywords: micronucleus formation in buccal mucosa, chemical exposure of genotoxic compounds, occupational riskAbstrak: Suatu pekerjaan dapat memiliki risiko dan bahaya terpapar senyawa kimia yang bersifat genotoksik. Senyawa kimia tersebut dapat menyebabkan terbentuknya mikronukleus di mukosa pipi rongga mulut. Penelitian ini bertujuan untuk mengulas pengaruh paparan senyawa kimia pada berbagai macam pekerjaan terhadap pembentukan mikronukleus di mukosa bukal. Jenis penelitian ialah literature review. Penelusuran literatur melalui database PubMed, ScienceDirect, dan Google Scholar berdasarkan kata kunci yang sesuai. Kriteria literatur ialah terbitan tahun 2016-2021 dengan Bahasa Indonesia atau Inggris. Hasil penelitian mendapatkan senyawa kelompok polycyclic aromatic hydrocarbon (PAH), logam, carbamate, dan organophospate, serta senyawa silica, benzene, toluene, xylene (BTX), sevoflurane, desflurane, isoflurane, nitrous oksida, gemcitabin, dan 5-fluoro uracil merupakan senyawa kimia yang bersifat genotoksik dan dapat memicu pembentukan mikronukleus di mukosa bukal mekanik, pemanggang daging, penambang, pendaur ulang sampah elektronik, pekerja konstruksi, pekerja marka jalan, pengecat mobil, petugas SPBU, petani dan tenaga kesehatan. Senyawa kimia yang bersifat genotoksik banyak ditemukan di lingkungan pekerjaan. Senyawa tersebut dapat merusak DNA sel sehingga terbentuk mikronukleus di mukosa bukal pekerja. Disarankan untuk melakukan penelitian lanjut mengenai biomarker kerusakan sel akibat paparan senyawa kimia yang genotoksik.Kata kunci: pembentukan mikronukleus di mukosa pipi, paparan senyawa kimia genotoksik, risiko pekerjaan

Micronuclei arising due to loss of KIF18A form stable micronuclear envelopes and do not promote tumorigenesis

Micronuclei, whole or fragmented chromosomes which are spatially separated from the main nucleus, are strongly associated with genomic instability and have been identified as drivers of tumorigenesis. Paradoxically, Kif18a mutant mice produce micronuclei due to unaligned chromosomes in vivo but do not develop spontaneous tumors, raising questions about whether all micronuclei contribute similarly to genomic instability and cancer. We report here that micronuclei in Kif18a mutant mice form stable nuclear envelopes. Challenging Kif18a mutant mice via deletion of the Trp53 gene led to formation of thymic lymphoma with elevated levels of micronuclei. However, loss of Kif18a had modest or no effect on survival of Trp53 homozygotes and heterozygotes, respectively. To further explore micronuclear envelope stability in KIF18A KO cells, we compared micronuclei induced via different insults in cultured cells. Micronuclei in KIF18A KO cells form stable nuclear envelopes characterized by increased recruitment of core and non-core nuclear envelope components and successful expansion of decondensing chromatin compared to those induced by microtubule drug washout or exposure to radiation. We also observed that lagging chromosomes, which lead to micronucleus formation, were positioned closer to the main chromatin masses, and further from the central spindle, in KIF18A KO cells. Our studies provide in vivo support to models suggesting that micronuclear fate depends on the sub-cellular location of late lagging chromosomes and suggest that not all micronuclei actively promote tumorigenesis.