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

Anticancer Res. 2021 Apr;41(4):1849-1858. doi: 10.21873/anticanres.14951.

Abstract

Background/aim: 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.

Materials and methods: 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.

Results: Cement particles, in concentrations not significantly reducing ex vivo proliferation according to mitotic index, dose-dependently increased micronuclei formation.

Conclusion: Through the establishment of an OECD guideline 487 conform MNA, we demonstrate the mutagenic effects of cement on human OPCs.

Keywords: Micronucleus assay; cement dust; oropharyngeal mucosa-derived primary epithelial cells.

MeSH terms

  • Cells, Cultured
  • Construction Materials / toxicity*
  • Dose-Response Relationship, Drug
  • Dust*
  • Epithelial Cells / drug effects*
  • Epithelial Cells / pathology
  • Female
  • Humans
  • Laryngeal Neoplasms / chemically induced
  • Laryngeal Neoplasms / pathology
  • Male
  • Micronuclei, Chromosome-Defective / chemically induced*
  • Micronucleus Tests
  • Mouth Mucosa / drug effects*
  • Mouth Mucosa / pathology
  • Primary Cell Culture
  • Risk Assessment
  • Squamous Cell Carcinoma of Head and Neck / chemically induced
  • Squamous Cell Carcinoma of Head and Neck / pathology

Substances

  • Dust