Early diagnostic value of cell-free DNA in sulfur mustard-induced acute lung injury
FAN Zhenpeng
SHI Minjie
GUO Xiaojie
LI Jiawei
ZHANG Yujiao
GAO Tian
WANG Changyan
CAO Meng
YU Weihua
LIU Jiangzheng
KONG Deqin
LI Wenli
Abstract：Objective To investigate the diagnostic value of cell-free DNA(cf-DNA)in acute lung injury induced by sulfur mustard(SM).Methods C57BL/6 mice were exposed to 80 mL/L of the SM simulator 2-chloroethyl ethyl sulfide(CEES)via nebulization inhalation.The effects of CEES on mouse body mass and lung-to-body weight ratio were examined.HE and TUNEL staining were used to assess changes in lung tissue structure and pulmonary cell apoptosis,respectively.Pulmonary function was evaluated using a whole-body plethysmography system.Protein concentration and cell count in bronchoalveolar lavage fluid(BALF)were measured by BCA protein assay and flow cytometry,respectively.Hematological parameters were analyzed using an automated hematology analyzer.Inflammatory factor concentrations in serum and BALF were determined using ELISA kits.Total cf-DNA concentration and cf-mtDNA copy number in serum and BALF were measured using a microspectrophotometer and a PCR instrument,respectively.Results Compared with the control group,the CEES-exposed group showed reduced body mass(P<0.01),disrupted lung tissue structure,increased lung-to-body weight ratio(P<0.01),decreased lung function(P<0.05),no significant differences in BALF cell count or protein concentration,no obvious pulmonary cell apoptosis by TUNEL staining,and normal hematological parameters.Serum and BALF levels of inflammatory factors IL-1β and TNF-α were significantly elevated(P<0.01).Serum total cf-DNA concentration showed no change,while serum cf-mtDNA copy number decreased(P<0.05).BALF total cf-DNA concentration significantly increased,and cf-mtDNA copy number also increased(P<0.05).Conclusion In SM-induced acute lung injury,before significant cell apoptosis or marked abnormalities in hematological parameters occur,BALF total cf-DNA concentration significantly increases,and cf-mtDNA copy numbers in serum and BALF change.These changes may serve as early detection indicators for SM exposure.
Keywords：sulfur mustardacute lung injurycell-free DNAearly diagnosisinflammationbronchoalveolar lavage fluidliquid biopsy2-chloroethyl ethyl sulfide
Publication Date：2026-05-31
Online Publishing Date：2026-08-26(First online date of this platform, not the publication date of the document)
Pages：7( 660-665,672 )