Toxicological and Carcinogenic Cellular Effects of High Molecular Weight Polycyclic Aromatic Hydrocarbons

Polycyclic aromatic hydrocarbons (PAHs) are omnipresent chemical compounds known to be associated with cancers via numerous molecular mechanisms. PAHs are known to increase cancer cell proliferation, migration, invasion as well as epithelial-mesenchymal transition. Among all PAHs, high molecular weight PAHs (HMW-PAHs) represent an important class due to their higher toxicity and longer persistence. The current article provides a systematic review encompassing toxicological and carcinogenic effects including in vitro and in vivo research findings reported during the last 15 years of nine HMW-PAHs belonging to the USEPA priority list (fluoranthene, pyrene, benzo(a)anthracene, chrysene, benzo(b)fluoranthene, benzo(a)pyrene, dibenzo(a,h)anthracene, indeno(1,2,3-cd)pyrene, and benzo(ghi)perylene). This study, for the first time, compiles research findings of different HMW-PAHs on one platform for better understanding of their mechanistic role. The current review indicates that HMW PAHs involved in DNA damage, epigenetic modifications, oxidative damage, imbalance in mitochondrial membrane potential, alterations in important protein levels, disproportion of immune components, dysregulation of gene expression, along with developmental and endocrine toxicities that are intricately involved in cancer. It is also found that although these compounds have similar structures, they show high mechanistic heterogeneity across compounds. However, the wide variation in experimental models among reported literature complicates the understanding of molecular mechanisms. Furthermore, the study recommends future research on various aspects of PAHs considering integrative and modern approaches. Taken together, the present study provides a foundational and comprehensive idea about HMW-PAHs, which will be helpful in future research to evaluate and mitigate the toxicities of PAHs.