Cytotoxic, genotoxic, and toxicogenomic effects of heated tobacco products and cigarette smoke in human primary keratinocytes.
Heated Tobacco Products
carcinogenesis
smoking
tobacco
Journal
Tobacco induced diseases
ISSN: 1617-9625
Titre abrégé: Tob Induc Dis
Pays: Greece
ID NLM: 101201591
Informations de publication
Date de publication:
2022
2022
Historique:
received:
08
03
2022
revised:
22
04
2022
accepted:
29
07
2022
entrez:
17
10
2022
pubmed:
18
10
2022
medline:
18
10
2022
Statut:
epublish
Résumé
Heated tobacco products (HTPs) appear to be less harmful to health than conventional cigarettes (CCs). However, limited analytical data are available to support this claim. This study aimed to compare the cytotoxic, genotoxic, and toxicogenomic effects of HTPs and CCs in carcinogenesis via multistep gene mutations in the oral mucosal cells. Cigarette smoke extract (CSE) was obtained from HTPs and CCs. Primary human oral keratinocytes (HOKs) were treated with 5% and 20% CSE from HTPs and CCs. Cell survival rate assays were performed after 6, 12, and 24 h. After 6 h, DNA double-strand breaks (DSBs) were evaluated using anti-γH2AX antibodies with immunohistochemistry. mRNAs expressions of mediator of DNA damage checkpoint 1 (MDC1) and ataxia telangiectasia and Rad3-related protein (ATR), were analyzed. Expressions of miR-22 and miR-185 were analyzed because miR-22 targets MDC1 and miR-185, ATR. The HOKs had equivalent survival rates after exposure to the same concentrations of CSE from CCs and HTPs. HTPs increased foci formation of γH2AX in HOKs, as did CCs (without CSE vs 20% HTP, p<0.05; without CSE vs 20% CC, p<0.05). Expressions of MDC1 and ATR decreased in cells exposed to CSE from CCs and HTPs (MDC1: without CSE vs 20% HTP, p<0.05; without CSE vs 20% CC, p<0.05; ATR: without CSE vs 20% HTP, p<0.05; without CSE vs 20% CC, p<0.05). Expressions of miR-22 and miR-185 were not significantly increased when exposed to CSE from CCs or HTPs. HTPs and CCs had similar cytotoxic effects. HTPs are genotoxic, can cause DSBs, and have toxicogenomic damage because they inhibit the MDC1 and ATR-CHK1 DNA repair pathways in the oral mucosa. The miRNA-mRNA axis was not related to these inhibitions.
Identifiants
pubmed: 36249345
doi: 10.18332/tid/152510
pii: 82
pmc: PMC9523519
doi:
Types de publication
Journal Article
Langues
eng
Pagination
82Informations de copyright
© 2022 Morishita Y. et al.
Déclaration de conflit d'intérêts
The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none was reported.
Références
J Hematol Oncol. 2019 Apr 24;12(1):43
pubmed: 31018854
J Oral Pathol Med. 2013 Apr;42(4):309-14
pubmed: 23173553
Nat Genet. 2001 Mar;27(3):247-54
pubmed: 11242102
Adv Dent Res. 2019 Oct;30(1):4-10
pubmed: 31538806
Cell. 2017 Feb 9;168(4):644-656
pubmed: 28187286
Toxicol In Vitro. 2019 Dec;61:104652
pubmed: 31526836
Nature. 2003 Feb 27;421(6926):961-6
pubmed: 12607005
Cell Death Dis. 2013 Jun 27;4:e699
pubmed: 23807228
ERJ Open Res. 2019 Feb 11;5(1):
pubmed: 30775377
Nicotine Tob Res. 2021 Nov 5;23(12):2127-2134
pubmed: 34036368
Cell Cycle. 2004 Aug;3(8):1062-8
pubmed: 15254392
Cancer Res. 2015 Apr 1;75(7):1298-310
pubmed: 25627978
Oral Oncol. 2018 Dec;87:165-169
pubmed: 30527233
Tob Control. 2017 Aug 4;:
pubmed: 28778971
Environ Sci Technol. 2016 Sep 6;50(17):9644-51
pubmed: 27461870
Regul Toxicol Pharmacol. 2016 Nov 30;81 Suppl 2:S27-S47
pubmed: 27720919
Int J Oncol. 2018 Mar;52(3):841-850
pubmed: 29393341
Nat Rev Cancer. 2008 Dec;8(12):957-67
pubmed: 19005492
Mutat Res. 2009 Aug;678(1):43-52
pubmed: 19591958
Proteomics. 2016 Feb;16(3):402-16
pubmed: 26572502
JAMA Intern Med. 2017 Jul 1;177(7):1050-1052
pubmed: 28531246
Science. 2016 Nov 4;354(6312):618-622
pubmed: 27811275
Regul Toxicol Pharmacol. 2018 Mar;93:14-33
pubmed: 29080848
IARC Monogr Eval Carcinog Risks Hum. 2004;83:1-1438
pubmed: 15285078
IARC Monogr Eval Carcinog Risks Hum. 2007;89:1-592
pubmed: 18335640
Tob Control. 2018 Nov;27(Suppl 1):s13-s19
pubmed: 30206183
Hum Pathol. 2014 Jan;45(1):17-26
pubmed: 24125744
Tob Control. 2018 Nov;27(Suppl 1):s30-s36
pubmed: 30158205
Cell. 2013 Mar 14;152(6):1344-54
pubmed: 23498941
Ann Lab Med. 2015 Mar;35(2):226-32
pubmed: 25729725
Nat Rev Mol Cell Biol. 2009 Feb;10(2):141-8
pubmed: 19145236
Trends Biochem Sci. 2010 Feb;35(2):101-8
pubmed: 19875294
Am J Respir Cell Mol Biol. 1998 Nov;19(5):819-25
pubmed: 9806747
J Tongji Med Univ. 1991;11(1):6-9
pubmed: 1875455
PLoS One. 2014 Aug 05;9(8):e103993
pubmed: 25093845
Tob Control. 2018 Nov;27(Suppl 1):s39-s40
pubmed: 30131373
Tob Control. 2020 Jun 29;:
pubmed: 32601147