Azathioprine and UVA Light Generate Mutagenic Oxidative DNA Damage
St Thomas' Hospital · Queen Mary University of London · +5 more institutions
Abstract
Oxidative stress and mutagenic DNA lesions formed by reactive oxygen species (ROS) are linked to human malignancy. Clinical treatments inducing chronic oxidative stress may therefore carry a risk of therapy-related cancer. We suggest that immunosuppression by azathioprine (Aza) may be one such treatment. Aza causes the accumulation of 6-thioguanine (6-TG) in patients' DNA. Here we demonstrate that biologically relevant doses of ultraviolet A (UVA) generate ROS in cultured cells with 6-TG-substituted DNA and that 6-TG and UVA are synergistically mutagenic. A replication-blocking DNA 6-TG photoproduct, guanine sulfonate, was bypassed by error-prone, Y-family DNA polymerases in vitro. A preliminary analysis…
Citation impact
- FWCI
- 27.36
- Percentile
- 100%
- References
- 27
Authors
10- POPeter O’Donovan
St Thomas' Hospital, Queen Mary University of London, King's College London, The Open University, Cancer Research UK, RIKEN, King's College School
- CMConal M. Perrett
St Thomas' Hospital, Queen Mary University of London, King's College London, The Open University, Cancer Research UK, RIKEN, King's College School
- XZXiaohong Zhang
St Thomas' Hospital, Queen Mary University of London, King's College London, The Open University, Cancer Research UK, RIKEN, King's College School
- BMBeatriz Montaner
St Thomas' Hospital, Queen Mary University of London, King's College London, The Open University, Cancer Research UK, RIKEN, King's College School
- YXYao−Zhong Xu
St Thomas' Hospital, Queen Mary University of London, King's College London, The Open University, Cancer Research UK, RIKEN, King's College School
Topics & keywords
- Azathioprine
- DNA damage
- DNA
- Oxidative phosphorylation
- Chemistry
- Oxidative damage
- Oxidative stress
- Biochemistry
- Good health and well-being