Cellular mechanisms of medium-chain chlorinated paraffins toxicity: the effect of cellular lipid content

Research on chlorinated paraffins (CPs) is growing, with accumulating evidence of CPs being present in biological matrices and animal tissues. However, their cellular-level impacts remain underexplored. This study investigates the effects of medium-chain CPs on adipose and liver cell models. The results show that CPs are more toxic at lower concentrations in 3T3-L1 preadipocytes than in adipocytes, suggesting that intracellular lipids may offer protection against these contaminants. However, neither simulated lipolysis in adipocytes nor lipogenesis in HepG2 hepatocytes revealed any lipid-dependent effects of CPs. CP exposure reduced heme oxygenase 1 expression, indicating a biological response to these contaminants. In a coculture model of adipocytes and macrophages, CP exposure influenced cell signaling, with lipid-rich adipocytes modulating macrophage immune responses. Our results demonstrate that medium-chain CPs accumulation in lipid-rich tissues does not significantly affect their toxic effects. However, it may influence cell signaling within adipose tissue.