Benzo[a]pyrene osteotoxicity, neurotoxicity, and epigenetic effects in fishes and mammals: a review

Polycyclic aromatic hydrocarbons are well-known pollutants, yet some apects of their osteotoxicity and neurotoxicity have not been reviewed. Here we review benzo[a]pyrene-induced osteotoxicity and neurotoxicity in fish and mammals, with focus on phenotypic changes, cell development, molecular signaling pathways, key gene expression, and epigenetic modifications. Benzo[a]pyrene impairs bone health by suppressing osteoblast formation, promoting bone resorption, and disrupting remodeling, primarily through dysregulation of key transcription factors and signaling pathways. In neural tissues, metabolically-activated benzo[a]pyrene generates reactive oxygen species, triggering oxidative stress, dysregulation of gene expression, mitochondrial dysfunction, altered neurotransmitter levels, and neuronal apoptosis. Benzo[a]pyrene induced multigenerational osteotoxicity in 42% of fish studies, but 0% in rodent studies. It induced multigenerational neurotoxicity in 25% of fish studies and 15% in rodent studies. Epigenetic modifications are a critical mechanism linking benzo[a]pyrene exposure to these multigenerational and transgenerational toxicity in bone and neural systems of both fish and rodents.