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Analysis of DNA and Hemoglobin Adducts and Sister Chromatid Exchanges in a Human Population Occupationally Exposed to Propylene Oxide

A Pilot Study

Department of Biosciences, Karolinska Institute, Novum, S-141 57 Huddinge, Sweden [K. C., D. S.]; Department of Molecular Biology and Functional Genomics, Stockholm University, S-106 91 Stockholm, Sweden [S. O-G., H. L. P.]; Medical Genetics Centre South-West Netherlands, Department of Radiation Genetics and Chemical Mutagenesis, Leiden University Medical Centre, 2300 RA Leiden, the Netherlands [X. Y., A. T. N.]; and Liaoning Institute of Occupational Health, Shenyang [G. L.], Huludao Chemicals Plant, Huludao [M. L.], and Huludao Institute of Occupational Health, Huludao [F. Z.], Liaoning province 110005, People’s Republic of China

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 ³²P-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/10⁹ 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.

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