Microplastic-induced carcinogenesis: Molecular mechanisms, cellular interactions, and toxicological implications.

Abstract

Microplastics (<5 mm) are widespread environmental contaminants, with increasing human exposure through ingestion, inhalation, and dermal contact. Their presence in terrestrial, aquatic, and atmospheric systems, along with detection in human tissues such as blood, lungs, placenta, and the gastrointestinal tract, highlights their bioavailability and potential health risks. Owing to their small size, high surface-area-to-volume ratio, and surface reactivity, microplastics can interact with biological molecules and cells, raising concerns about their role in disease development. This review presents a mechanistic perspective on microplastic-induced carcinogenesis. Microplastics can enter the body via multiple routes and disrupt cellular homeostasis by inducing oxidative stress, chronic inflammation, mitochondrial dysfunction, and genotoxicity. These effects contribute to genomic instability and dysregulation of key signaling pathways, including NF-κB, MAPK, and PI3K/Akt, which are associated with tumor initiation and progression. Additionally, microplastics act as "Trojan horse" carriers, facilitating the transport of co-contaminants such as heavy metals, persistent organic pollutants, and microbial agents, thereby enhancing their bioavailability and toxicity. The combined effects of microplastics and associated toxicants amplify oxidative stress, inflammatory responses, and epigenetic alterations, promoting a pro-tumorigenic environment. Despite growing evidence, significant knowledge gaps remain regarding long-term exposure, the behavior of nanoplastics in biological systems, and their direct link to cancer. This review emphasizes the need for integrated and interdisciplinary research to better understand microplastic-associated carcinogenesis and to support effective risk assessment and regulatory strategies.