An evaluation of styrene genotoxicity using several biomarkers in a 3-yearfollow-up study of hand-lamination workers

A study employing several biomarkers of styrene exposure and genotoxicity w as carried out in a group of lamination (reinforced plastic) workers and co ntrols, who had been repeatedly sampled during a 3-year period. Special att ention will be paid to the last sampling (S. VI), reported here for the fir st time. Styrene concentration in the breathing zone, monitored by personal dosimeters, and urinary mandelic acid (MA) were measured as indicators of external exposure. Blood samples were assayed for styrene-specific O-6-guan ine adducts in DNA, N-terminal valine adducts of styrene in haemoglobin, DN A single-strand breaks (SSB), determined by use of the single cell gel elec trophoresis (Comet) assay), and hypoxanthine guanine phosphoribosyl transfe rase (HPRT) mutant frequencies (MF) in T-lymphocytes. O-6-styrene guanine a dduct levels were significantly higher in the exposed group (5.9 +/- 4.9 ad ducts/10(8) dNp) as compared to laboratory controls (0.7 +/- 0.8 adducts/10 (8) dNp; P = 0.001). DNA adduct levels significantly correlated with haemog lobin adducts, SSB parameters and years of employment. Styrene-induced N-te rminal valine adducts were detected in the lamination workers (1.7 +/- 1.1 pmol/g globin), but not in the control group (detection limit 0.1 pmol/g gl obin). N-terminal valine adducts correlated strongly with external exposure indicators, DNA adducts and HPRT MF, No significant correlation was found with SSB parameters. A statistically significant difference in HPRT MF was observed between the laminators (22.3 +/- 10.6/10(6)) and laboratory contro ls (14.2 +/- 6.5/10(6), P = 0.039), HPRT MF in the laminators significantly correlated with styrene concentration in air, MA and haemoglobin adducts, as well as with years of employment and age of the employees. No significan t difference (P = 0.450) in RIF between the laminators and the factory cont rols was observed. Surprisingly, we detected differences in MF between sexe s. When data from all measurements were combined, women showed higher MF (g eometric mean 15.4 vs. 11.2 in men, P = 0.020). The styrene-exposed group e xhibited significantly higher SSB parameters (tail moment (TM), tail length (TL) and the percentage of DNA in the tail (TP)) than the control group (P < 0.001). SSB parameters correlated with indicators of external exposure a nd with O-6-styrene guanine adducts. No significant correlation was found b etween SSB parameters and haemoglobin adducts or HPRT MF. The data encompas sing biomarkers from repented measurements of the same population over a 3- year period are discussed with respect to the mechanisms of genotoxic effec ts of styrene and the interrelationship of individual biomarkers. (C) 1999 Elsevier Science B.V. All rights reserved.