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

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.

• Authors: Sun Woo Jin, Jong Seung Im, Jae Hyeon Park, Hyung Gyun Kim, Gi Ho Lee, Se Jong Kim, Seung Jun Kwack, Kyu-Bong Kim, Kyu Hyuck Chung, Byung Mu Lee, Sam Kacew, Hye Gwang Jeong, Hyung Sik Kim
• Journal: Journal of toxicology and environmental health. Part A (J Toxicol Environ Health A) Vol. 84 Issue 24 Pg. 1004-1019 (12 17 2021) ISSN: 1528-7394 [Print] England
• PMID: 34459362 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Carcinogens
• Nitrosamines
• 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone

Topics

• Animals
• Biomarkers, Tumor (genetics)
• Carcinogenesis (chemically induced, genetics, metabolism, pathology)
• Carcinogens (analysis, toxicity)
• DNA Methylation (drug effects)
• Epigenesis, Genetic (drug effects)
• Epigenome (drug effects)
• Gene Expression (drug effects)
• Lung (drug effects, metabolism, pathology)
• Lung Neoplasms (chemically induced, genetics, metabolism, pathology)
• Mice
• Nitrosamines (analysis, toxicity)
• Tobacco Smoking (adverse effects)