Use of human thyroid cell primary cultures for genotoxicity studies

Abstract

Primary cultures of human thyroid cells prepared from fragments discarded during the course of prescribed surgery were examined for their sensitivity to the DNA-damaging activity of selected chemicals in order to assess if they can represent a reliable model for genotoxicity studies. DNA fragmentation was measured by the alkaline elution technique. Positive dose-related responses in the range of subtoxic concentrations were obtained after 1 hr of exposure to the direct-acting alkylating agents N-nitroso- N-methylurea (0.3–3 m m), N-nitroso- Nethylurea (1–10 m m), methyl methanesulphonate (0.1–1 m m) and ethyl methanesulphonate (1–10 m m). In contrast, any meaningful evidence of DNA fragmentation was absent in cultures exposed for 20 hr to N-nitrosodimethylamine (1–100 m m) and N-nitrosodiethylamine (10–100 m m). This suggests that in human thyroid cells the level of mixed-function oxidase activity is not sufficient to give rise to effective concentrations of the reactive species of the latter two procarcinogens.