DNA-protein crosslinks and p53 protein expression in relation to occupational exposure to formaldehyde

Background: Formaldehyde (FA) is classified as a probable human carcinogen. Aims: To examine DNA protein crosslinks (DPC) and p53, which are generally known to be involved in carcinogenesis, in peripheral blood lymphocytes of workers exposed to FA. Methods: DPC and p53 (wild type and mutant) were examined in peripheral blood lymphocytes of 186 workers exposed to FA (mean years of exposure=16) and 213 unexposed workers. Every worker completed a questionnaire on demographic data, occupational and medical history, smoking, and hygiene. Results: The adjusted mean level of DPC in the exposed and the unexposed workers differed significantly. Adjustment was made for age, sex, years of education, smoking, and origin. Exposure to FA increased the risk of having a higher level of pantropic p53 above 150 pg/ml (OR 1.6, 95% CI 0.8 to 3.1). A significant positive correlation was found between the increase of pantropic p53 protein and mutant p53 protein, as well as between pantropic p53>150 pg/ml and mutant p53 protein. In the exposed group a significantly higher proportion of p53>150 pg/ml was found among workers with DPC>0.187 (55.7%) (0.187=median level of DPC) than among workers with DPC less than or equal to0.187 (33.3%).The risk of having a pantropic p53 protein >150 pg/ml was determined mainly by levels of DPC. Workers with DPC above the median level had a significantly higher risk of having pantropic p53 >150 pg/ml (adjusted OR 2.5, 95% CI 1.2 to 5.4). Conclusions: Results suggest that DPC and mutation in p53 may represent steps in FA carcinogenesis and a possible causal relation between DPC and mutation in p53. These biomarkers can be applied in the assessment of the development of cancer due to FA exposure.