Cytotoxic and genotoxic evaluation of cotinine using human neuroblastoma cells (SH-SY5Y)

Abstract Cotinine is the main metabolite of nicotine, which is metabolized in the liver through a cytochrome P450 enzyme. Different studies point to genetic instability caused by nicotine, such as single and double DNA strand breaks and micronuclei formation, but little is known about the effect of...

Full description

Bibliographic Details
Main Authors: Daiana Dalberto, Caroline Cardoso Nicolau, Ana Leticia Hilario Garcia, Adriane Perachi Nordin, Ivana Grivicich, Juliana da Silva
Format: Article
Language:English
Published: Sociedade Brasileira de Genética
Series:Genetics and Molecular Biology
Subjects:
Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572020000400501&lng=en&tlng=en
_version_ 1818341915334017024
author Daiana Dalberto
Caroline Cardoso Nicolau
Ana Leticia Hilario Garcia
Adriane Perachi Nordin
Ivana Grivicich
Juliana da Silva
author_facet Daiana Dalberto
Caroline Cardoso Nicolau
Ana Leticia Hilario Garcia
Adriane Perachi Nordin
Ivana Grivicich
Juliana da Silva
author_sort Daiana Dalberto
collection DOAJ
description Abstract Cotinine is the main metabolite of nicotine, which is metabolized in the liver through a cytochrome P450 enzyme. Different studies point to genetic instability caused by nicotine, such as single and double DNA strand breaks and micronuclei formation, but little is known about the effect of cotinine. Therefore, the present in vitro study assessed the effects of cotinine on cell viability and DNA damage in SH-SY5Y neuroblastoma cells, as well as genotoxicity related to oxidative stress mechanisms. Comparisons with nicotine were also performed. An alkaline comet assay modified by repair endonucleases (FPG, OGG1, and Endo III) was used to detect oxidized nucleobases. SH-SY5Y neuronal cells were cultured under standard conditions and exposed for 3 h to different concentrations of cotinine and nicotine. Cytotoxicity was observed at higher doses of cotinine and nicotine in the MTT assay. In the trypan blue assay, cells showed viability above 80% for both compounds. Alkaline comet assay results demonstrated a significant increase in damage index and frequency for cells treated with cotinine and nicotine, presenting genotoxicity. The results of the enzyme-modified comet assay suggest a DNA oxidative damage induced by nicotine. Unlike other studies, our results demonstrated genotoxicity induced by both cotinine and nicotine. The similar effects observed for these two pyridine alkaloids may be due to the similarity of their structures.
first_indexed 2024-12-13T16:06:23Z
format Article
id doaj.art-fecbe6445fe3426190c4f93d124f4bb2
institution Directory Open Access Journal
issn 1415-4757
1678-4685
language English
last_indexed 2024-12-13T16:06:23Z
publisher Sociedade Brasileira de Genética
record_format Article
series Genetics and Molecular Biology
spelling doaj.art-fecbe6445fe3426190c4f93d124f4bb22022-12-21T23:39:02ZengSociedade Brasileira de GenéticaGenetics and Molecular Biology1415-47571678-468543210.1590/1678-4685-gmb-2019-0123S1415-47572020000400501Cytotoxic and genotoxic evaluation of cotinine using human neuroblastoma cells (SH-SY5Y)Daiana DalbertoCaroline Cardoso NicolauAna Leticia Hilario GarciaAdriane Perachi NordinIvana GrivicichJuliana da SilvaAbstract Cotinine is the main metabolite of nicotine, which is metabolized in the liver through a cytochrome P450 enzyme. Different studies point to genetic instability caused by nicotine, such as single and double DNA strand breaks and micronuclei formation, but little is known about the effect of cotinine. Therefore, the present in vitro study assessed the effects of cotinine on cell viability and DNA damage in SH-SY5Y neuroblastoma cells, as well as genotoxicity related to oxidative stress mechanisms. Comparisons with nicotine were also performed. An alkaline comet assay modified by repair endonucleases (FPG, OGG1, and Endo III) was used to detect oxidized nucleobases. SH-SY5Y neuronal cells were cultured under standard conditions and exposed for 3 h to different concentrations of cotinine and nicotine. Cytotoxicity was observed at higher doses of cotinine and nicotine in the MTT assay. In the trypan blue assay, cells showed viability above 80% for both compounds. Alkaline comet assay results demonstrated a significant increase in damage index and frequency for cells treated with cotinine and nicotine, presenting genotoxicity. The results of the enzyme-modified comet assay suggest a DNA oxidative damage induced by nicotine. Unlike other studies, our results demonstrated genotoxicity induced by both cotinine and nicotine. The similar effects observed for these two pyridine alkaloids may be due to the similarity of their structures.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572020000400501&lng=en&tlng=encotininenicotinecytotoxicitygenotoxicitysh-sy5y cells
spellingShingle Daiana Dalberto
Caroline Cardoso Nicolau
Ana Leticia Hilario Garcia
Adriane Perachi Nordin
Ivana Grivicich
Juliana da Silva
Cytotoxic and genotoxic evaluation of cotinine using human neuroblastoma cells (SH-SY5Y)
Genetics and Molecular Biology
cotinine
nicotine
cytotoxicity
genotoxicity
sh-sy5y cells
title Cytotoxic and genotoxic evaluation of cotinine using human neuroblastoma cells (SH-SY5Y)
title_full Cytotoxic and genotoxic evaluation of cotinine using human neuroblastoma cells (SH-SY5Y)
title_fullStr Cytotoxic and genotoxic evaluation of cotinine using human neuroblastoma cells (SH-SY5Y)
title_full_unstemmed Cytotoxic and genotoxic evaluation of cotinine using human neuroblastoma cells (SH-SY5Y)
title_short Cytotoxic and genotoxic evaluation of cotinine using human neuroblastoma cells (SH-SY5Y)
title_sort cytotoxic and genotoxic evaluation of cotinine using human neuroblastoma cells sh sy5y
topic cotinine
nicotine
cytotoxicity
genotoxicity
sh-sy5y cells
url http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572020000400501&lng=en&tlng=en
work_keys_str_mv AT daianadalberto cytotoxicandgenotoxicevaluationofcotinineusinghumanneuroblastomacellsshsy5y
AT carolinecardosonicolau cytotoxicandgenotoxicevaluationofcotinineusinghumanneuroblastomacellsshsy5y
AT analeticiahilariogarcia cytotoxicandgenotoxicevaluationofcotinineusinghumanneuroblastomacellsshsy5y
AT adrianeperachinordin cytotoxicandgenotoxicevaluationofcotinineusinghumanneuroblastomacellsshsy5y
AT ivanagrivicich cytotoxicandgenotoxicevaluationofcotinineusinghumanneuroblastomacellsshsy5y
AT julianadasilva cytotoxicandgenotoxicevaluationofcotinineusinghumanneuroblastomacellsshsy5y