Dr. Volker Arlt & Prof. David Phillips in paper published 16th January in Mutagenesis: use of the Muta™Mouse system to critically examine the health risks associated with tissue-specific adduct loads.
Prof. David Phillips & Dr. Volker Arlt, King’s College London, Analytical and Environmental Sciences Division, MRC-PHE Centre for Environment and Health, are authors in a paper published in Mutagenesis entitled, "Quantitative relationships between lacZ mutant frequency and DNA adduct frequency in Muta™Mouse tissues and cultured cells exposed to 3-nitrobenzanthrone"
Previously, they employed the Muta™Mouse system to examine the induction of lacZ mutants and DNA adducts following exposure to the wellstudied mutagenic carcinogen 3-nitrobenzanthrone (3-NBA). In this follow-up work, they examined the empirical relationships between total adduct frequency and mutant frequency (MF) in tissues and cultured cells following acute 3-NBA exposure.
The results show a significant induction of DNA damage and lacZ mutants in liver, colon and bone marrow, as well as FE1 pulmonary epithelial cells. In contrast, lung and small intestine samples had low, but significantly elevated adduct levels, with no significant increases in lacZ MF. Additional analyses showed a significant relationship between the mutagenic efficiency of total adducts, measured as the slope of the relationships between MF and total adduct frequency, and tissue-specific mitotic index (MI).
The work provides a proof of principle regarding the use of the Muta™Mouse system to critically examine the health risks associated with tissue-specific adduct loads.