Mutagenesis Advance Access published online on August 4, 2008
Mutagenesis, doi:10.1093/mutage/gen040
Factors affecting the incidence of genotoxicity biomarkers in peripheral blood lymphocytes: impact on design of biomonitoring studies
1Health Protection Agency, c/o DH Wellington House, 133–155 Waterloo Road, London SE1 8UG, UK 2DH Toxicology Unit, Imperial College London, Hammersmith Campus, London W12 0NN, UK 3Health Protection Agency, Chilton, Didcot, Oxon OX11 0RQ, UK
A review of risk factors affecting background rates of micronuclei and chromosomal aberration (CA) formation in peripheral blood lymphocytes (PBLs) was undertaken with a view to aiding the interpretation of genotoxicity biomonitoring studies. Both endogenous factors and those due to methodological variation were evaluated. Background variation of other indices of genotoxicity in PBLs (specifically 8-hydroxy-deoxyguanosine and comet assays) were also considered as these data likely reflect overlapping causes of DNA damage and may provide some indicators for future research areas. A number of host risk factors, namely age, gender, smoking, vitamin B12 and folate status, were identified for which there is strong or sufficient evidence that they impact on background levels of genotoxicity biomarkers. Evaluation of these factors should be routinely included in genotoxicity biomonitoring studies. Although data on the influence of smoking is somewhat inconsistent, because of its known association with cancer and DNA damage, it is also classified as a high-risk factor. A number of other factors were identified for which there is weak or insufficient evidence including alcohol consumption, disease conditions and infections, physical exercise, body mass index and genotype. The review shows that the evaluation of biomonitoring studies of genotoxicity is complex and there is a need to improve study designs by setting an a priori hypothesis, collecting good exposure data and stratifying groups appropriately, using appropriate power calculations before initiating biomonitoring studies, and collecting information on appropriate risk factors. There is a need for further collaborative work and the establishment of centres of excellence on genotoxicity biomonitoring. If these measures are achieved, then it would be possible to use the data from biomonitoring studies in risk assessments to derive risk management measures.
* To whom correspondence should be addressed. Tel: +44 207 972 4076; Fax: +44 207 972 1001; Email: jon.battershill{at}dh.gsi.gov.uk
Received on April 3, 2008; revised on July 3, 2008; accepted on July 3, 2008.