Science
99 Exploring the Impact of Medicines on DNA Repair Enzymes
Mary Fairbanks and Martin Horvath (School Of Biological Sciences)
Faculty Mentor: Martin Horvath (School of Biological Sciences, University of Utah)
Abstract
Medicines are known to alter the gut’s microbiome composition and function, but their ability to also impact DNA repair enzymes has not yet been investigated. In this study, we added medicines into bacterial systems to see how mutation rate and DNA repair enzymes were impacted. We found that aspirin was toxic to bacteria and determined a tolerable dose through bacterial growth rate tests. A concentration of 0.01 mg/mL of aspirin showed the same replication rate as when no medicine was added, so we kept the dose below this threshold to maintain a level playing field for the following mutation suppression assay. The mutation frequency rates of bacteria exposed with various concentrations of medicines were measured through counting rifampicin resistant mutants that spontaneously arose in an overnight culture. The median mutation rate for aspirin was 22 per 100 million cells plated (14-29, 95% confidence interval; CI), which was not significantly different from the rate measured for water at 23 (19-28, 95% CI). Similarly, the median mutation rate for adapalene was 19.5 (16-28, 95% CI), which was not significantly different from the rate measured for DMSO at 24.5 (21-33, 95% CI). These results show that aspirin and adapalene do not impact mutation rates in our laboratory strain of bacteria. Previous studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) increase the likelihood of infection from Clostridioides difficile by diminishing microbiome diversity and resistance, which raises concerns about medicines negatively impacting the microbiome. Our results reassure us that medicines like aspirin and adapalene probably do not have off-target impacts on DNA repair enzymes, and thus are unlikely to disrupt the mutation rate of bacteria in our microbiome.
Introduction
Commonly used medicines treat specific symptoms or illnesses but may have unintended side effects. Aspirin is taken to reduce pain and fever but is sometimes used to prevent heart attacks and ischemic strokes (strokes that occur when the flow of blood to the brain is blocked) (Brazier 2020). Aspirin belongs to a group of medicines called salicylates, which stop the production of certain natural substances that cause fever, pain, swelling, and blood clots. A rare side effect of daily low-dose aspirin is hemorrhagic stroke (Brazier 2020). Other side effects of aspirin include irritation of the stomach lining and digestive problems (Zimlich 2022). Variations in drug outcomes encourage us to investigate pathways at a molecular level in order to improve drug-targeting efficiency, reduce side effects, and uncover hidden uses. Drug disposition (absorption, distribution, metabolism, and excretion) and pharmacokinetics (the rate of these processes and concentration com