Effects of tobacco compound 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) on the expression of epigenetically regulated genes in lung carcinogenesis. Issue 24 (17th December 2021)

• Record Type: Journal Article
• Authors: Jin, Sun Woo; Im, Jong Seung; Park, Jae Hyeon; Kim, Hyung Gyun; Lee, Gi Ho; Kim, Se Jong; Kwack, Seung Jun; Kim, Kyu-Bong; Chung, Kyu Hyuck; Lee, Byung Mu; Kacew, Sam; Jeong, Hye Gwang; Kim, Hyung Sik
• Is Part Of: Journal of toxicology and environmental health. Volume 84:Issue 24(2021)
• Page Start: 1004
• Page End: 1019
• Publication Date: 2021-12-17
• Subjects: Smoking -- NNK -- DNA methylation -- histone acetylation -- lung carcinogenesis; Toxicology -- Periodicals; Environmental health -- Periodicals; 615.90205
• DOI: 10.1080/15287394.2021.1965059
• Languages: English
• ISSNs: 1528-7394

Abstract

ABSTRACT: Cigarette smoking is a major cause of lung cancer. Although tobacco smoking-induced genotoxicity has been well established, there is apparent lack of abundance functional epigenetic effects reported On cigarette smoke-induced lung carcinogenesis. The aim of this study was to determine effects of intratracheal administration of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) utilizing target gene expression DNA methylation patterns in lung tissues of mice following twice weekly for 8 weeks treatment. An unbiased approach where genomic regions was undertaken to assess early methylation changes within mouse pulmonary tissues. A methylated-CpG island recovery assay (MIRA) was performed to map the DNA methylome in lung tissues, with the position of methylated DNA determined using a Genome Analyzer (MIRA-SEQ). Alterations in epigenetic-regulated target genes were confirmed with quantitative reverse transcription-PCR, which revealed 35 differentially hypermethylated genes including Cdkn1C, Hsf4, Hnf1a, Cdx1, and Hoxa5 and 30 differentially hypomethylated genes including Ddx4, Piwi1, Mdm2, and Pce1 in NNK-exposed lung tissue compared with controls. The main pathway of these genes for mediating biological information was analyzed using the Kyoto Encyclopedia of Genes and Genomes database. Among them, Rssf1 and Mdm2 were closely associated with NNK-induced lung carcinogenesis. Taken together, our data provide valuable resources for detecting cigarette smoke-induced lung carcinogenesis.