P-32-post-labelling of 7-(3-chloro-2-hydroxypropyl)guanine in white blood cells of workers occupationally exposed to epichlorohydrin

Epichlorohydrin (ECH) is a simple 3-carbon epoxide of industrial importance . It has been shown to be genotoxic in several systems and carcinogenic in experimental animals. The aim of the present investigation was to study DNA adducts of ECH as a biomarker of occupational exposure to this chemical. 7 -(3-Chloro-2-hydroxypropyl)guanine (7-CHP-guanine) was analysed in DNA from white blood cells using an anion exchange-based adduct enrichment protocol of the P-32-post-labelling/HPLC-based assay. Blood samples were collected from seven workers handling ECH (exposed), nine workers not handling ECH bu t normally present in the premises where this chemical is used (potentially exposed) and 13 office and factory workers from locations in the plant whe re ECH is not handled (controls), 7-CHP-guanine was detected in five of the seven workers exposed to ECH (1.6-7.1 mol/10(9) mol nucleotides) and in tw o of the nine workers potentially exposed to ECH (0.8-1.5 mol/10(9) mol nuc leotides), This adduct was not detected in any of the 13 controls. The diff erence in adduct levels between exposed workers and controls was statistica lly significant (Mann-Whitney test, P < 0.001), as was the difference betwe en exposed workers and potentially exposed workers (P = 0.017), The recover y of 7-CHP-guanine in the P-32-post-labelling assay was on average 48 +/- 7 %, which is considerably higher than previously reported for other 7-alkylg uanines, The method used had a limit of detection of similar to 0.4 mol add uct/10(9) mol nucleotides using 20 mu g DNA, This study shows for the first time ECH induced DNA adducts in humans and suggests that 7-CHP-guanine may be used as a biomarker of occupational exposure to ECH.