THE RESPONSE OF RENAL TUBULAR EPITHELIAL-CELLS TO PHYSIOLOGICALLY ANDCHEMICALLY-INDUCED GROWTH ARREST

Cells respond to a variety of stresses by activating the transcription of a battery of ''acute phase'' or ''stress response'' genes. The nat ure of this response is tailored to the nature of the stress. The exte nt to which physiologically and pathophysiologically induced growth ar rest share common genomic responses is unclear. We therefore compared the effects of a physiologically induced (serum and nutrient depletion ) and a chemically induced (2-Br-bis-(GSyl)HQ and 2-Br-6-(GSyl)HQ) str ess in renal tubular epithelial cells (LLC-PK1). The response to physi ological stress, induced by serum depletion, involves growth arrest ch aracterized by an inhibition of DNA synthesis that occurs in the absen ce of a decrease in histone mRNA or an increase in gadd153 mRNA, one o f the growth arrest and DNA damage inducible genes. In contrast, the c hemical-induced stress involves growth arrest accompanied by a decreas e in histone mRNA, particularly core histone H2B and H2A mRNA, and the induction of gadd153. Chemical-induced changes in histone mRNA invers ely correlate to changes in the expression of a stress gene, hsg70, wh ose expression is dependent upon the maintenance of appropriate nucleo somal structure.