Abstract: By metal-like toxic substance-arsenic exposure to the skin fibroblasts of Liaoning cashmere goats, the toxic effects of arsenic on cashmere goat skin fibroblasts and the mechanism of inducing cell apoptosis were explored, which aimed to provide a theoretical basis for further studying the growth effects of arsenic on cashmere goat skin cells. One 7-month-old male Liaoning new line cashmere goat with normal functions and the weight of about 25 kg was randomly selected, its abdominal skin was taken and the cells were cultured. The dimethyl arsenic acid was formulated into 11 different concentration groups (0, 0.1, 0.2, 0.4, 0.8, 1,5, 10, 25, 50, 100 mmol·L^-1), and 3×10⁴cells·mL^-1 skin cells were exposed to the drug for 24, 48, 72, and 96 h. After repeating the experiment by MTT method for 3 times, the proliferation and inhibition of cashmere goat skin fibroblasts were detected, the time points and 4 concentration groups(Control, Promotion, Critical, 50% inhibitory concentration (IC₅₀)) for the subsequent experiment were set up.The changes of cytoskeleton, cytoplasm and organelle were observed by immunofluorescence and TEM (transmission electron microscopy), respectively. The comet assay was used to detect DNA damage. Flow cytometry (FCM) was used to detect the changes of cell apoptosis. The mitochondrial transmembrane potential (ΔΨm) and the number of lysosomes were observed and analyzed by the staining intensity of the fluorescent dye Mito-Tracker Green. The OD values of different concentrations at 24 h could clearly reflect the proliferation and inhibition trend of dimethyl arsenic acid on cashmere goat skin fibroblasts, while the proliferation effect at 48, 72, and 96 h was gradually weakened or even disappeared, and the cell proliferation and inhibition effect was the best at 24 h.Therefore, the control group (without any treatment), the promotion group (0.8 mmol·L^-1), the critical group (1 mmol·L^-1), and the IC₅₀ group(38.68 mmol·L^-1) for 24 h were selected. Based on all results, when skin fibroblasts were treated with dimethyl arsenic acid(0.1-1 mmol·L^-1) for 24 h, the cytoskeleton was intact, the cell DNA was not tailed, and the apoptosis rate was low, the number of mitochondria increased, the membrane structure was clear, the cristae was dense, the morphology was complete, the membrane potential and the number of lysosomes increased. When the concentration of dimethyl arsenic acid was greater than 1 mmol·L^-1, it inhibited the growth of cashmere goat skin fibroblasts and caused obvious cytotoxicity (P<0.01), at the same time, the cytoskeleton morphology changed, the DNA was not tailed, the apoptotic rate significantly increased, the mitochondria swollen, the morphology was irregular shape, the cristae was broken and dissolved, the membrane potential reduced, and the number of lysosomes reduced. The cytoskeleton morphology of IC₅₀group was very different, and cometary tails were most obvious in the DNA of the cells(P<0.01), the number of apoptosis significantly increased, the membrane potential significantly decreased(P<0.01), and the number of lysosomes significantly decreased (P<0.01). In this study, the toxic effect of dimethyl arsenic acid on the skin fibroblasts of Liaoning cashmere goats and the mechanism of inducing cell apoptosis were explored, which indicated that a certain concentration of dimethyl arsenic acid had a toxic effect on the skin fibroblasts of Liaoning cashmere goats and further induced apoptosis.

Key words: dimethyl arsenic acid, Liaoning cashmere goat, skin fibroblasts, cell proliferation, apoptosis