The core strength of this group at present is in technological development linked with application of novel methods to topics in human health and disease – the area known as molecular epidemiology.
The ESCODD project which I coordinated examined the causes of the enormous variation in estimates of the background level of DNA oxidation in human cells. As a result of this project, it is now accepted that about 1 in a million bases are oxidised (1000x less than many previous estimates) (Ref. 2).
In vitro assay
An in vitro assay for base excision repair (BER) of oxidised DNA was developed (Ref. 1), as a modification of the comet assay – a technique in which we have acquired an international reputation (Refs 4, 7). We subsequently adapted the assay to measure nucleotide excision repair (NER) of UV-induced damage, and reported the wide range of activities seen in healthy subjects (Ref. 10).
Our collaborator Jana Slyskova has now successfully modified the technique to measure BER and NER capacity of normal and tumour tissue from colorectal cancer patients.
Protective effects of fruits and vegetables
In human intervention studies (crossover design), we demonstrated protective effects of fruits and vegetables ( Refs 3, 5). Protection occurs at the level of enhanced antioxidant status, and increased DNA repair activity (a novel finding). Support for these in vivo findings comes from experiments in cell culture: Ref. 9 reports the effects of β-cryptoxanthin on DNA oxidation and DNA repair in HeLa and Caco2 cells.
Our methods have wide applications in human biomonitoring (Ref. 8). Of particular interest is the possibility to search for links between genotype and phenotype (Ref. 6).