DIFFERENTIAL INDUCTION OF GROWTH ARREST INDUCIBLE GENES BY SELENIUM-COMPOUNDS

The effects of two types of selenium compounds on the expression level s of growth arrest and DNA damage-inducible (gadd) genes and on select ed cell death genes were examined in mouse mammary MOD cells to test t he hypothesis that the diversity of selenium-induced cellular response s to these compounds could be distinguished by unique gene expression patterns. Whereas the expression patterns of known cell death-related genes (bcl-2 and bax) were not informative with respect to the cellula r response patterns upon exposure to selenium compounds, time-dependen t and selenium species-specific induction patterns were observed for g add34, gadd45 and gadd153 genes. It was also observed that the MOD cel ls expressed a truncated p53 transcript but no detectable immunoreacti ve P53 protein, indicating a null p53 phenotype. The fact that seleniu m compounds induced growth arrest and death of these cells and that th ese compounds induced specific patterns of expression of gadd genes in dicates that these genes may mediate some selenium-induced cellular re sponses. The findings further imply that selenium compounds may be eff ective chemopreventive agents for human breast carcinogenesis, in whic h p53 mutations are frequent. (C) 1997 Elsevier Science Inc.