Mutational signatures of genome-modified Caenorhabditis elegans expressing the human cytochrome P450 (CYP1A1 and CYP1A2) pathway

Polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (BaP), are produced by the incomplete combustion of organic matter and thus are present in tobacco smoke, charbroiled food and diesel exhaust. The nematode Caenorhabditis elegans lacks the genetic components of the classical mammalian cytochrome P450 (CYP)-mediated BaP-diol-epoxide metabolism pathway thus CYP1A1 or CYP1A2 together with human epoxide hydrolase (EPHX) was introduced into the worm genome, thereby allowing to study potential physiological, genomic and transcriptional changes after BaP exposure in these CYP-humanised C. elegans strains. Whole genome sequencing revealed a higher frequency of T>G base substitution mutations in worms expressing human CYP1A1;EPHX thereby demonstrating the amenity of introducing human genes into the C. elegans genome and their utility to serve as a model for environmental carcinogenesis and pharmacological research. Whole genome sequencing was carried out via the Illumina NovaSeq platform to detect SNPs, InDels, SVs and CNVs in C.elegans exposed to no, a low (40 µM) or high (640 µM) concentrations of benzo[a]pyrene from synchronized L1 stage to L4 stage. Three strains were used , namely a background strain, or strains that were genome-modified to express either the human CYP1A1 and EPHX or CYP1A2 and EPHX .