Chemical Transformation of Human Keratinocytes by 2,3,7,8-Tetrachlorodibenxo-ρ-dioxin

2,3,7,8-Tetrachlorodibenzo-ρ-dioxin (TCDD) is a ubiquitous, persistent environmental contaminant and the most powerful carcinogen categorized by IARC. Although the mechanism of carcinogenesis by TCDD is poorly understood, several studies have shown that the skin is one of target organs for TCDD. In this study, we investigated the neoplastic transformation of human keratinocyte-derived cell line, HaCaT, by chemical transformation method using N-methyl-N'-nitro-N-nitorsoguanidine (MNNG) and TCDD. We found that subsequent exposure to TCDD for 3 weeks after initial exposure to MNNG markedly induced transformed cells. It was suggested that TCDD can act as a potent promoter in HaCaT cells. Furthermore, these transformed cells showed morphological alternations in soft agar and increased telomerase activity. Therefore, the TCDD treatment of HaCaT cells by initiated with MNNG could promote neoplastic transformation without stimulation by exogenous growth factors. As a result, TCDD had a strong potency as a promoter in nontumorigenic immortalized human epidermal keratinocytes.