title: Cytotoxicity and gene expression profiling of polyhexamethylene guanidine hydrochloride in human alveolar A549 cells.
abstract: In Korea, lung disease of children and pregnant women associated with humidifier disinfectant use has become a major concern. A common sterilizer is polyhexamethylene guanidine (PHMG), a member of the guanidine family of antiseptics. This study was done to elucidate the putative cytotoxic effect of PHMG and the PHMG-mediated altered gene expression in human alveolar epithelial A549 cells in vitro. Cell viability analyses revealed the potent cytotoxicity of PHMG, with cell death evident at as low as 5 μg/mL. Death was dose- and time-dependent, and was associated with formation of intracellular reactive oxygen species, and apoptosis significantly, at even 2 μg/mL concentration. The gene expression profile in A549 cells following 24 h exposure to 5 μg/mL of PHMG was investigated using DNA microarray analysis. Changes in gene expression relevant to the progression of cell death included induction of genes related to apoptosis, autophagy, fibrosis, and cell cycle. However, the expressions of genes encoding antioxidant and detoxifying enzymes were down-regulated or not affected. The altered expression of selected genes was confirmed by quantitative reverse transcription-polymerase chain reaction and Western blot analyses. The collective data suggest that PHMG confers cellular toxicity through the generation of intracellular reactive oxygen species and alteration of gene expression.
authors.affiliation: Department of Microbiology, College of Medicine, Soonchunhyang University, South Korea.
authors.forename: Ha-Na
authors.initials: HN
authors.lastname: Jung
authors.affiliation: Department of Microbiology, College of Medicine, Soonchunhyang University, South Korea.
authors.forename: Tamanna
authors.initials: T
authors.lastname: Zerin
authors.affiliation: Department of Microbiology, College of Medicine, Soonchunhyang University, South Korea.
authors.forename: Biswajit
authors.initials: B
authors.lastname: Podder
authors.affiliation: Department of Microbiology, College of Medicine, Soonchunhyang University, South Korea. Electronic address: songmic@sch.ac.kr.
authors.forename: Ho-Yeon
authors.initials: HY
authors.lastname: Song
authors.affiliation: Department of Microbiology, College of Medicine, Soonchunhyang University, South Korea. Electronic address: yongsikkim@sch.ac.kr.
authors.forename: Yong-Sik
authors.initials: YS
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006146:Guanidines / Q000633:toxicity*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000187:drug effects*
chemical_list: D006146:Guanidines; C060540:polyhexamethyleneguanidine
keywords: Apoptosis; Cytotoxicity; Microarray; Polyhexamethylene guanidine; ROS