Initiating carcinogen, triethylenemelamine, induces micronuclei in skin target cells.

Keratinocytes from mouse skin were cultured for a short period in vitro following single or multiple treatments at low dose levels in vivo with the known chromosome-damaging agent triethylenemelamine (TEM). The chemical was applied to the skin of HRA/Skh hairless mice at concentrations corresponding to those reported to initiate cancer in initiation-promotion assays. A significant dose-related depression in keratinocyte cell recovery occurred over the dose range 0.3-1 mg TEM/mouse (single or multiple treatments). Under the same conditions, a dose-related induction of micronuclei was observed using the cytokinesis-block method with cytochalasin B. A similar frequency of micronuclei was detected in binucleate cells from mice treated with single or multiple applications of TEM. Mice held for 12-48 h post-treatment, before removal of skin for in vitro culture, yielded highest micronuclei frequencies. These results indicate that the same target cell population, skin keratinocytes, can be used to investigate both genotoxicity and carcinogenesis, and that micronucleus induction in these cells may be a sensitive signal of skin cancer initiation.