摘要Background:Nickel-induced allergic contact dermatitis (Ni-ACD) is a global health problem.More detailed knowledge on the skin uptake of haptens is required.This study aimed to investigate the penetration process and distribution of nickel in skin tissues with late phase and early phase of Ni-ACD to understand the mechanisms of metal allergy.Methods:Forty Hartley guinea pigs were divided into four groups according to the NiSO4 sensitizing concentration and the NiSO4 challenged concentration:the 5 ％ NiSO4-group,5 ％ to 10 ％ (sensitization-challenge;late phase group);10％ NiSO4-group,10％ to 10％ (sensitization-challenge;early-phase group);and the positive and negative controls.Pathological biopsies were performed on each group.The depth profile of nickel element concentration in the skin of guinea pigs was detected by synchrotron radiation micro X-ray fluorescence spectroscopy (SR-μ-XRF) and micro X-ray absorption near-edge spectroscopy (μ-XANES).Results:In each section,the nickel element concentration in both the 5％ NiSO4-group and 10％ NiSO4-group was significantly higher than that in the negative control group.In the upper 300-μm section of skin for the early phase group,the nickel element concentration was significantly higher than that in the lower section of skin.In deeper sections (＞200 μm) of skin,the concentration of nickel in the early phase group was approximately equal to that in the late phase group.The curve of the late phase group was flat,which means that the nickel element concentration was distributed uniformly by SR-μ-XRF.According to the XANES data for the 10％ NiSO4 metal salt solution,structural changes occurred in the skin model sample,indicating that nickel was not present in the Ni2+ aqueous ionic state but in the nickel-binding protein.Conclusions:This study showed that the distribution of the nickel element concentration in ACD skin tissue was different between the early phase and late phase groups.The nickel element was not present in the Ni2+ aqueous ionic state but bound with certain proteins to form a complex in the stratum corneum in ACD model tissue.