An application of the challenge assay in boat builders exposed to low levels of styrene – a feasibility study of a possible biomarker for acquired susceptibility

Abstract

Abstract Sensitivity to carcinogens and susceptibility for malignant diseases may be related to genetic predisposition, e. g. polymorphisms in toxicant-metabolizing enzymes or DNA repair deficiencies. The latter may also be acquired by exposure to substances that interfere with DNA repair processes. Application of the challenge assay to an exposed population may allow scientists to study the interference of DNA repair as an acquired susceptibility phenomenon. The assay was therefore used in a feasibility study to evaluate its application. A group of 14 workers exposed to low levels of styrene (mean < 100 mg/m 3 styrene in air; 35 μg/l styrene in blood) and a reference of seven controls were investigated for structural chromosomal aberrations using FISH. The rate of exchange-type aberrations per 100 metaphases was 0.14 (95% CI, 0.05–0.31) in controls and 0.22 (95% CI, 0.13–0.36) in exposed workers. The difference is not statistically significant. Interaction with DNA repair was measured in the 14 workers and 2 historical controls using the challenge assay. Exchange-type aberrations per 100 metaphases after X-ray challenge of 1.66 Gy were 13.26 (10.53–16.50) and 16.19 (15.00–17.40) for the controls and exposed, respectively. The difference is statistically significant (p < 0.038). Among the exposed group, the challenge response was also significantly correlated with the cumulative lifetime exposure to styrene (R 2 = 0.3996; p < 0.015) but not with the current exposure as measured in blood (R 2 = 0.0226; p = 0.700). The challenge responses in the short-term and long-term exposed subgroups were 15.55 (14.23–16.96) and 17.90 (15.64–20.39), respectively, based on sample sizes of 5 and 9, respectively. The difference was not significant. Hence, data from our study is consistent with the hypothesis that long-term exposure to styrene can interfere with DNA repair activities. The lack of statistical differences in some of the data may be due to the small sample size and a possible confounding by age in our investigation. Additional data from our ongoing study should clarify this uncertainty.