Abstract
Circadian variations in immune defense and tissue repair may interfere with shift effects of occupational exposure when investigating biomarkers in cross-shift studies. This investigation compared biomarkers of inflammation and DNA damage in 59 nonsmoking and 59 smoking male construction workers pre- (6–10 a.m.) versus postshift (4–7 p.m.). Cellular compositions were analyzed in blood, induced sputum (IS), and nasal lavage fluid (NALF) and soluble inflammatory biomarkers were analyzed in IS and NALF. DNA damage was measured as 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) adducts and DNA strand breaks (alkaline Comet assay) in white blood cells (WBC). Apoptosis was quantified as percent apoptotic cells by annexin V and 7-amino-actinomycin staining in blood lymphocytes using flow cytometry. In nonsmokers higher preshift than postshift levels of interleukin-8 (IL-8) in IS and more DNA strand breaks were detected. However, more DNA adducts were found postshift. Among smokers, the cellular composition of IS and NALF differed between pre- and postshift samples, in particular more neutrophils pre- than postshift. In contrast, more cells in early apoptosis were observed post shift in both smokers and nonsmokers. These results indicate a potential influence of circadian rhythms on several biomarkers used in epidemiological studies. Data suggest interference with shift-work effects of occupational exposure in cross-shift studies and also the need to consider smoking as a modifying variable.
Acknowledgments
This study is part of the Human Bitumen Study, which was initiated by the German Committee for Hazardous Substances (AGS) and the German Bitumen Forum and financially supported by German Social Accident Insurance (DGUV), Eurobitume, Deutscher Asphaltverband e.V., Concawe, Zentralverband des Deutschen Dachdeckerhandwerks, Industrieverband Bitumen-, Dach- und Dichtungsbahnen e.V., Berufsgenossenschaft Rohstoffe und Chemische Industrie (BG RCI) and Aksys GmbH, Beratungsstelle Gussasphaltanwendungen (bga), BG BAU, Arbeitsgemeinschaft der Bitumenindustrie (Arbit). We thank all workers who participated in the Human Bitumen Study. We gratefully acknowledge the support of the field team, especially Anne Flagge, Anja Molkenthin, Bianca Wachter, Dieter Höber, Gerd Zoubek, and in parts of the study Klaus Schott (†) and Hans-Jürgen Schicker and the laboratory staff Gerda Borowitzki, Susanne Freundt, Heike Stubel, Maria Düser Sabine Bernard, Evelyn Heinze, Sigrid Reckinger-Pospiech, and Helga Hut for their skilful technical assistance.