Coal Tar-Based Driveway Sealant Extract Induces Mutations in Liver, Bone Marrow, and Germ Cells of MutaMouse Male Mice

Abstract

Coal tar-based driveway sealants (CTS) are a widespread but underrecognized source of human exposure to mutagenic polycyclic aromatic hydrocarbons (PAHs). We used Duplex Sequencing, an error-corrected sequencing technology, to assess the mutagenicity of a complex PAH mixture extracted from a CTS in MutaMouse male mice. We observed significant dose-dependent increases in mutation frequency (MF) in liver and bone marrow, with mutation spectra dominated by C:G > A:T substitutions, closely resembling a mutational signature linked to human cancers associated with tobacco smoking. In germ cells, we did not observe a statistically significant increase in MF, although there was a positive dose–response trend and enrichment of C:G > A:T mutations at higher doses. The mutagenic effects of CTS in germ cells were supported by a statistically significant increase in mutant frequency measured using the plaque-based lacZ assay. Tissue-specific analyses revealed greater mutation susceptibility and potency in liver, likely reflecting its central role in PAH metabolism. Mutation spectrum analysis showed that the mutagenic profile of the CTS extract largely resembled that of benzo(a)pyrene; however, detailed spectral analysis indicated additional contributions from other PAHs or PAH metabolites that produced distinct mutational patterns. Collectively, our findings demonstrate that the CTS extract induces tissue-specific mutagenic responses driven by characteristic C:G > A:T mutations, offering mechanistic insight into how environmental PAH mixtures contribute to mutation burden and cancer risk.