Micronucleus Formation in Primary Oropharyngeal Epithelial Cells Reveals Mutagenicity of Cement Dusts.

Abstract

Epidemiological studies showed an increased risk of developing laryngeal head and neck squamous cell carcinoma (HNSCC) for employees working in the construction business. This suggested a causal link between exposure to cement particles and development of HNSCC but data were missing. We established an Organisation for Economic Co-operation and Development (OECD) guideline 487-conform micronucleus assay (MNA) using oropharyngeal mucosa-derived primary epithelial cells (OPCs) ex vivo. OPCs from healthy mucosa of 52 donors were cultured in vitro and incubated with serial concentrations of two common cement particles. Mitomycin C was used as a soluble positive control, and TiO2 and DQ12 were used as negative and positive particle controls. Bi-nucleated cells were counted and the mitotic index (MI) was determined. Subsequently, micronuclei-containing bi-nucleated cells (MN+) were counted. Cement particles, in concentrations not significantly reducing ex vivo proliferation according to mitotic index, dose-dependently increased micronuclei formation. Through the establishment of an OECD guideline 487 conform MNA, we demonstrate the mutagenic effects of cement on human OPCs.