Sung Hwa Jung, Jeong Sang Hoon, Kang Ja Young, Kim Cherry, Nam Yoon Jeong, Kim Jae Young, Choi Jin Young, Lee Hye Jin, Lee Yu Seon, Kim Eun Yeob, Baek Yong Wook, Lee Hong, Lee Ju Han
Department of Oncology and Hematology, Ansan Hospital, Korea University College of Medicine, Ansan-si 15355, Gyeonggi, Republic of Korea.
Medical Science Research Center, Ansan Hospital, Korea University College of Medicine, Ansan-si 15355, Gyeonggi, Republic of Korea.
Toxics. 2022 Nov 16;10(11):694. doi: 10.3390/toxics10110694.
Polyhexamethylene guanidine phosphate (PHMG-p), the main ingredient of humidifier disinfectants, circulates systemically through the lungs; however, its toxicological assessment has been primarily limited to pulmonary disease. Herein, we investigated the possible abnormalities in hematopoietic function 20 weeks after intratracheal instillation of PHMG-p in a rat model. Notable abnormalities were found out in the peripheral blood cell count and bone marrow (BM) biopsy, while RNA sequencing of BM tissue revealed markedly altered gene expression. Furthermore, signaling involved in hematopoietic dysfunction was predicted by analyzing candidate genes through Ingenuity Pathway Analysis (IPA) program. Respiratory PHMG-p exposure significantly decreased monocyte and platelet (PLT) counts and total protein, while significantly increasing hemoglobin and hematocrit levels in peripheral blood. Histopathological analysis of the BM revealed a reduced number of megakaryocytes, with no significant differences in spleen and liver weight to body weight. Moreover, PHMG-p exposure significantly activated estrogen receptor signaling and RHOA signaling, and inhibited RHOGDI signaling. In IPA analysis, candidate genes were found to be strongly related to 'hematological system development and function' and 'hematological disease.' Accordingly, our results suggest that PHMG-p could affect hematopoiesis, which participates in monocyte differentiation and PLT production, and may induce hematologic diseases via the respiratory tract.
聚六亚甲基胍磷酸盐（PHMG-p）是加湿器消毒剂的主要成分，可通过肺部在全身循环；然而，其毒理学评估主要局限于肺部疾病。在此，我们在大鼠模型中研究了气管内滴注PHMG-p 20周后造血功能可能出现的异常。在外周血细胞计数和骨髓活检中发现了明显异常，而骨髓组织的RNA测序显示基因表达明显改变。此外，通过 Ingenuity Pathway Analysis（IPA）程序分析候选基因，预测了造血功能障碍所涉及的信号通路。呼吸道暴露于PHMG-p显著降低了外周血中的单核细胞和血小板（PLT）计数以及总蛋白，同时显著提高了血红蛋白和血细胞比容水平。骨髓的组织病理学分析显示巨核细胞数量减少，脾脏和肝脏重量与体重无显著差异。此外，PHMG-p暴露显著激活了雌激素受体信号通路和RHOA信号通路，并抑制了RHOGDI信号通路。在IPA分析中，发现候选基因与“血液系统发育和功能”以及“血液疾病”密切相关。因此，我们的结果表明，PHMG-p可能影响造血功能，参与单核细胞分化和PLT生成，并可能通过呼吸道诱发血液疾病。
