title: Analysis of genomic responses in a rat lung model treated with a humidifier sterilizer containing polyhexamethyleneguanidine phosphate.
abstract: The antimicrobial biocide polyhexamethyleneguanidine (PHMG) phosphate is the main ingredient in the commercially available humidifier disinfectant. PHMG phosphate-based humidifier disinfectants can cause pulmonary fibrosis and induce inflammatory and fibrotic responses both in vivo and in vitro. However, toxicological mechanisms including genomic alterations induced by inhalation exposure to PHMG phosphate have not been elucidated. Therefore, this study evaluated the toxicological effects of the PHMG phosphate-containing humidifier disinfectant. We used DNA microarray to identify global gene expression changes in rats treated with PHMG phosphate-containing humidifier disinfectant for 4 weeks and 10 weeks. Functional significance of differentially expressed genes (DEGs) was estimated by gene ontology (GO) analysis. Four weeks post-exposure, 320 and 392 DEGs were identified in female and male rats, respectively (>2-fold, p<0.05). Ten weeks post-exposure, 1290 and 995 DEGs were identified in females and males, respectively. Of these, 119 and 556 genes overlapped between females and males at 4 weeks and 10 weeks, respectively, post-PHMG phosphate exposure. In addition, 21 genes were upregulated and 4 genes were downregulated in response to PHMG phosphate in a time-dependent manner. Thus, we predict that changes in genomic responses could be a significant molecular mechanism underlying PHMG phosphate toxicity. Further studies are required to determine the detailed mechanism of PHMG phosphate-induced pulmonary toxicity.
authors.affiliation: Department of Inhalation Toxicology Research, Korea Institute of Toxicology, Jeonbuk 56212, Republic of Korea.
authors.forename: Min-Seok
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Department of Research and Development, Genoplan Inc., Seoul 06221, Republic of Korea.
authors.forename: Seok Won
authors.initials: SW
authors.lastname: Jeong
authors.affiliation: Department of Inhalation Toxicology Research, Korea Institute of Toxicology, Jeonbuk 56212, Republic of Korea.
authors.forename: Seong-Jin
authors.initials: SJ
authors.lastname: Choi
authors.affiliation: Department of Inhalation Toxicology Research, Korea Institute of Toxicology, Jeonbuk 56212, Republic of Korea; Department of Human and Environmental Toxicology, University of Science & Technology, Daejeon, 34113, Republic of Korea.
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Han
authors.affiliation: Department of Inhalation Toxicology Research, Korea Institute of Toxicology, Jeonbuk 56212, Republic of Korea.
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon, 34114, Republic of Korea; Department of Human and Environmental Toxicology, University of Science & Technology, Daejeon, 34113, Republic of Korea.
authors.forename: Seokjoo
authors.initials: S
authors.lastname: Yoon
authors.affiliation: Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon, 34114, Republic of Korea; Department of Human and Environmental Toxicology, University of Science & Technology, Daejeon, 34113, Republic of Korea.
authors.forename: Jung-Hwa
authors.initials: JH
authors.lastname: Oh
authors.affiliation: Department of Inhalation Toxicology Research, Korea Institute of Toxicology, Jeonbuk 56212, Republic of Korea; Department of Human and Environmental Toxicology, University of Science & Technology, Daejeon, 34113, Republic of Korea. Electronic address: khlee@kitox.re.kr.
authors.forename: Kyuhong
authors.initials: K
authors.lastname: Lee
mesh_terms: D000818:Animals; D004202:Disinfectants / Q000633:toxicity*; D004866:Equipment Contamination / Q000517:prevention & control*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D006146:Guanidines / Q000633:toxicity*; D000068998:Humidifiers; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011014:Pneumonia / Q000139:chemically induced* / Q000235:genetics; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000235:genetics; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D043922:Toxicogenetics / Q000379:methods
chemical_list: D004202:Disinfectants; D006146:Guanidines; C060540:polyhexamethyleneguanidine
keywords: Biomarkers; DNA microarray; Humidifier disinfectant; PHMG phosphate; Pulmonary disease