[Epigenetic changes in the promoter of the fragile histidine triad (FHIT) gene in human sebocytes under the influence of in vitro culture]. / Epigenetische Veränderungen am Promotor des fragilen Histidin-Trias(FHIT)-Gens in menschlichen Sebozyten unter dem Einfluss der In-vitro-Kultur.

ABSTRACT

BACKGROUND: Due to the lack of tumor suppressor function of the fragile histidine triad (FHIT) gene product, sebaceous gland carcinomas can develop. OBJECTIVE: The model of the sebocyte cell line SZ95 was used to identify methylated CpG islands at the 5'-end of the FHIT gene and the decrease of gene expression as well as the increase of double-stranded (ds) DNA breaks were examined. MATERIAL AND METHODS: Methylation, immunofluorescence analysis, promotor sequencing and treatment of SZ95 cells with 5­azacytidine/trichostatin A (TSA). RESULTS: The cultivation was accompanied by an increasing methylation of the CpG islands, a decrease of the FHIT gene expression and an accumulation of ds-DNA breaks. Treatment with 5­azacytidine/TSA showed a decrease in DNA methylation and a re-expression of FHIT transcripts. DISCUSSION: Epigenetic changes in the cellular genome are caused by in vitro cell culture. Consequently, a positive selection of sebocytes with an epigenetically inactivated FHIT locus occurs.