PMID- 35576221
OWN - NLM
STAT- MEDLINE
DCOM- 20220519
LR  - 20231213
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 17
IP  - 5
DP  - 2022
TI  - Tobacco-specific nitrosamine 1-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-4-butanal 
      (NNA) causes DNA damage and impaired replication/transcription in human lung 
      cells.
PG  - e0267839
LID - 10.1371/journal.pone.0267839 [doi]
LID - e0267839
AB  - Thirdhand smoke (THS) is a newly described health hazard composed of toxicants, 
      mutagens and carcinogens, including nicotine-derived tobacco specific 
      nitrosamines (TSNAs), one of which is 
      1-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-4-butanal (NNA). Although TSNAs are 
      generally potent carcinogens, the risk of NNA, which is specific to THS, is 
      poorly understood. We recently reported that THS exposure-induced adverse impact 
      on DNA replication and transcription with implications in the development of 
      cancer and other diseases. Here, we investigated the role of NNA in THS 
      exposure-induced harmful effects on fundamental cellular processes. We exposed 
      cultured human lung epithelial BEAS-2B cells to NNA. The formation of DNA base 
      damages was assessed by Long Amplicon QPCR (LA-QPCR); DNA double-strand breaks 
      (DSBs) and NNA effects on replication and transcription by immunofluorescence 
      (IF); and genomic instability by micronuclei (MN) formation. We found increased 
      accumulation of oxidative DNA damage and DSBs as well as activation of DNA damage 
      response pathway, after exposure of cells to NNA. Impaired S phase progression 
      was also evident. Consistent with these results, we found increased MN formation, 
      a marker of genomic instability, in NNA-exposed cells. Furthermore, ongoing RNA 
      synthesis was significantly reduced by NNA exposure, however, RNA synthesis 
      resumed fully after a 24h recovery period only in wild-type cells but not in 
      those deficient in transcription-coupled nucleotide excision repair (TC-NER). 
      Importantly, these cellular effects are common with the THS-exposure induced 
      effects. Our findings suggest that NNA in THS could be a contributing factor for 
      THS exposure-induced adverse health effect.
FAU - Sarker, Altaf H
AU  - Sarker AH
AUID- ORCID: 0000-0001-6868-8460
AD  - Biological Systems and Engineering Division, Lawrence Berkeley National 
      Laboratory, Berkeley, CA, United States of America.
FAU - Hang, Bo
AU  - Hang B
AD  - Biological Systems and Engineering Division, Lawrence Berkeley National 
      Laboratory, Berkeley, CA, United States of America.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220516
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (1-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-4-butanal)
RN  - 0 (Aldehydes)
RN  - 0 (Carcinogens)
RN  - 0 (Nitrosamines)
RN  - 0 (Pyridines)
RN  - 0 (Tobacco Smoke Pollution)
RN  - 63231-63-0 (RNA)
RN  - 6M3C89ZY6R (Nicotine)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Aldehydes
MH  - Carcinogens/analysis
MH  - DNA
MH  - DNA Damage
MH  - Genomic Instability
MH  - Humans
MH  - Lung/metabolism
MH  - Nicotine/analysis
MH  - *Nitrosamines/analysis/toxicity
MH  - Pyridines
MH  - RNA
MH  - Nicotiana/metabolism
MH  - *Tobacco Smoke Pollution/adverse effects/analysis
PMC - PMC9109921
COIS- The authors have declared that no competing interests exist.
EDAT- 2022/05/17 06:00
MHDA- 2022/05/20 06:00
PMCR- 2022/05/16
CRDT- 2022/05/16 13:34
PHST- 2021/12/15 00:00 [received]
PHST- 2022/04/14 00:00 [accepted]
PHST- 2022/05/16 13:34 [entrez]
PHST- 2022/05/17 06:00 [pubmed]
PHST- 2022/05/20 06:00 [medline]
PHST- 2022/05/16 00:00 [pmc-release]
AID - PONE-D-21-39486 [pii]
AID - 10.1371/journal.pone.0267839 [doi]
PST - epublish
SO  - PLoS One. 2022 May 16;17(5):e0267839. doi: 10.1371/journal.pone.0267839. 
      eCollection 2022.