Relationship between Asbestos Exposures and 8-Hydroxydeoxyguanosine Levels in Leukocytic DNA of Workers at a Chinese Asbestos-material Plant.

Abstract

The objective of the study was to evaluate the level of 8-hydroxydeoxyguanosine (8-OHdG) in DNA of peripheral-blood leukocytes as a biological marker of asbestos exposure and/or its fibrotic effects in an occupational population exposed to asbestos. The setting was a large-scale asbestos plant in China producing brake linings, asbestos rubber, and textile using chrysotile. From a base population of active and retired workers with various levels of cumulative exposure to asbestos and grades of asbestosis, 39 study subjects were randomly selected to reflect incremental grades of asbestosis based on Chinese diagnostic standards. They consisted of 19 "normal" (control) and ten "suspected" and ten "definite" asbestosis-grade subjects, group-matched for age and sex. Leukocytic DNA was extracted from 5-mL samples of peripheral blood and 8-OHdG level measured by high-pressure liquid chromatography. A cumulative asbestos exposure index (CEI) was calculated for each subject as the summed product of duration and level of asbestos exposure per job, incorporating a job-exposure matrix. Geometric mean 8-OHdG levels showed a positive gradient in relation to increasing grades of asbestosis (control: 1.78, suspected: 2.21, definite: 2.58), with a significant difference between the control and definite-asbestosis subgroups (p < 0.05). The 8-OHdG level of the two subgroups combined as one "asbestosis" group was significantly higher than that of the control group (control: 1.78, asbestosis: 2.39, p = 0.01). Further, 8-OHdG levels were moderately correlated with CEIs for all subjects (r = 0.35, p < 0.05) and with grades of asbestosis for all (r = 0.47, p < 0.01) and for male subjects (r = 0.43, p < 0.05). In multiple regression analyses, grade of asbestosis explained 27% of the total variation in 8-OHdG and was a better predictor than CEI or duration of exposure. Thus, the 8-OHdG level in leukocytic DNA is related to grade of asbestosis and to individual cumulative exposure and may serve as a biologic marker reflecting the status of oxidative DNA damage by asbestos.