Do microplastics (MPs) and nanoplastics (NPs) directly contribute to human carcinogenesis?

Microplastics (MPs; 0.1-5000 μm) and nanoplastics (NPs; 1-1000 nm) are ubiquitous contaminants that can enter the human body through the mouth, nose, and skin, where they bioaccumulate in many organs and tissues. The role of MPs/NPs in carcinogenesis is still largely unknown, despite mounting evidence linking them to DNA damage, cellular stress, and inflammation. The toxicokinetic and toxicodynamic mechanisms-absorption, distribution, and molecular interactions-by which MPs/NPs may cause or contribute to cancer are the aim of this review, which provides the first thorough, multidisciplinary investigation of this topic. By combining epidemiological, in vitro, and in vivo data, we are able to discover molecular pathways that may link exposure to carcinogenesis, such as transcription factor modulation and autophagy dysregulation. This review highlights the need for targeted research and coordinated regulatory action to limit the long-term health impact of MPs/NPs by redefining them as possible oncogenic agents in addition to environmental pollutants by emphasizing knowledge gaps and novel molecular targets. This review aims to provide a comprehensive, multidisciplinary synthesis of current knowledge on MPs/NPs to shed light on the toxicokinetic and toxicodynamic processes-absorption, distribution, cellular, and molecular interactions-that may underlie their potential carcinogenicity. In order to establish causation, this review further suggests giving priority to longitudinal epidemiology, physiologically relevant dose setting, and human-relevant mechanistic platforms (organoids, organs-on-chips, and multi-omics).