Formation of DNA adducts is a key event for a genotoxic mode of action and their presence is often used as a surrogate for mutation and increased cancer risk. Interest in DNA adducts are twofold: first, to demonstrate exposure, and second, to link DNA adduct location to subsequent mutations or altered gene regulation. Methods have been established to quantitate DNA adducts with high chemical specificity, and to visualize the location of DNA adducts, elegant bio-analytical methods have been devised utilizing enzymes, various chemistries, and molecular biology methods. Traditionally, these highly specific methods cannot be combined, and the results are incomparable. Initially developed for single-molecule DNA sequencing, nanopore-type technologies are expected to enable simultaneous quantitation and location of DNA adducts across the genome. Therefore, we evaluated the commercially available Oxford Nanopore Technology (ONT) sequencing platform for site-specific detection of DNA adducts and for distinguishing DNA adducts differing in sizes and regiochemistries. Using a panel of ~20 DNA adduct containing plasmids, the positions of DNA adducts were correctly identified and individual DNA adducts were clearly distinguished from each other. A limit of detection one adducts per 10^9 unmodified nucleotides is easily archived using 1ug DNA as staring material.

Mapping and distinguishing endogenous from exogenous DNA adducts using third generation single molecule sequencing

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.