Propylene oxide (PO), a simple
alkylating agent used in the chemical industry, is weakly genotoxic and induces nasal cavity
tumors in rodents on inhalation at high air concentrations.
DNA adducts,
hemoglobin adducts, and sister chromatid exchanges (SCE) were analyzed as
biomarkers of exposure in a group of eight PO-exposed workers and eight nonexposed subjects. 1-2-Hydroxypropyladenine (1-HP-adenine) in
DNA of WBCs was analyzed using a hypersensitive (32)P-postlabeling assay. HP-
valine in
hemoglobin was measured using gas chromatography/tandem mass spectrometry. Air measurements indicated PO levels in the range of 1-7 ppm. All three
biomarkers showed significantly increased levels in the exposed workers. 1-HP-adenine was recorded in seven of the exposed workers (mean 0.66 mol/10(9) mol
nucleotides) but was not detected in any of the control subjects. HP-
valine was found in all subjects (means of 2.7 and 0.006 pmol/mg
globin in exposed workers and controls, respectively). The average frequencies of SCE were 3.7/cell in exposed workers and 2.0/cell in controls, respectively.
DNA and
hemoglobin adducts were correlated (r = 0.887), as well as
DNA adducts and SCE (r = 0.792) and
hemoglobin adducts and SCE (r = 0.762). The present study is the first demonstrating PO-
DNA adducts in human individuals. It is also the first study indicating cytogenetic effects in humans from PO exposure, although confounding effects from other sources cannot be excluded.