Evaluation of the genotoxic effects caused by short-term oral administration of SiNPs with different porosities in mice
Author
Benito, Irene Gimeno
Term
4. term
Education
Publication year
2018
Submitted on
2018-06-01
Pages
53
Abstract
Syntetiske amorfe silica-nanopartikler (SiNPs) anvendes bredt, bl.a. som fødevaretilsætningen E551, hvilket gør vurdering af deres mulige genotoksiske effekter i mave-tarm-kanalen relevant. Denne masteropgave undersøger, om kortvarig oral eksponering for SiNPs med forskellig porøsitet kan forårsage DNA-skade i mus. Fire typer SiNPs (porøse og ikke-porøse; nominelle størrelser 100 nm og 300 nm) blev administreret ved to doser (100 mg/kg og 1000 mg/kg) via gavage, og effekter blev evalueret i jejunum ved dag 6 og dag 26. DNA-skade blev kvantificeret med den in vivo alkaliske comet-assay, der måler DNA-strengbrud i individuelle celler; forsøgsopsætningen blev forud valideret, og dispersions/aggregeringstilstande af SiNPs blev karakteriseret med TEM. Resultaterne viste ingen stigning i haleintensitet for nogen nanopartikler sammenlignet med vehikelkontrol ved hverken dag 6 eller dag 26. Under de undersøgte korttidsbetingelser fremkaldte de testede SiNPs således ingen detekterbar genotoksicitet i jejunum med comet-assayet. Fundene understreger behovet for yderligere studier af længerevarende eksponeringer og andre målorganer for at fuldstændigt vurdere risici.
Synthetic amorphous silica nanoparticles (SiNPs) are widely used, including as the food additive E551, making it important to assess their potential genotoxic effects in the gastrointestinal tract. This thesis evaluates whether short-term oral exposure to SiNPs with different porosities induces DNA damage in mice. Four SiNP types (porous and non-porous; nominal sizes 100 nm and 300 nm) were administered by gavage at two doses (100 mg/kg and 1000 mg/kg), and effects were assessed in the jejunum at day 6 and day 26. DNA damage was quantified using the in vivo alkaline comet assay, which measures strand breaks in individual cells; the assay setup was validated beforehand, and the dispersion/aggregation state of SiNPs was examined by TEM. No increase in tail intensity was observed for any nanoparticle compared with the vehicle control at either time point. Under these short-term exposure conditions, the tested SiNPs did not produce detectable genotoxicity in the jejunum by the comet assay. These findings highlight the value of further studies with longer exposure durations and additional target tissues to complete the risk assessment.
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