HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Tables All Versions of this Article: 8/2/115    most recent 00064.2001v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Casey, W. Articles by Morgan, K. Search for Related Content PubMed PubMed Citation Articles by Casey, W. Articles by Morgan, K.

Brief Communication

Transcriptional and physiological responses of HepG2 cells exposed to diethyl maleate: time course analysis

¹ Toxicogenomics
² Molecular Biochemistry
³ Oncology Biology, GlaxoSmithKline, Research Triangle Park, North Carolina 27709

Expression levels of 767 genes were measured in HepG2 cells at eight time points (0, 0.5, 1, 6, 12, 16, 20, and 24 h) following exposure to the oxidizing agent, diethyl maleate (DEM). DEM treatment caused an immediate and sustained loss of intracellular GSH, with a concomitant increase in GSSG. From 6–12 h after exposure, there was a substantial increase in the percentage of cells undergoing S phase arrest and apoptosis. Expression profiles of 90% of the genes fell into one of five clusters generated using hierarchical-clustering software, indicating the well-ordered nature of the stress response. The directional movement and timing of induction for many genes matched closely the known physiological role of the proteins they encode. Inhibitors of the cell cycle (CDKN1, CDKN4D, ATM) were induced, whereas cyclins [proliferating cell nuclear antigen (PCNA), cyclin A, cyclin D1, cyclin K] were downregulated during the period from 6–20 h. Likewise, pro-apoptotic genes such as the caspases (CASP9, CASP3, CASP2) and apoptotic protease activating factor (APAF) were induced during the same period. Results of this study indicate that there is a good correlation between time-dependant physiological, biochemical, and gene expression data.

cell cycle; apoptosis

This article has been cited by other articles:

				K. T. Morgan, M. Pino, L. M. Crosby, Min Wang, T. C. Elston, Z. Jayyosi, M. Bonnefoi, and G. Boorman Complementary Roles for Toxicologic Pathology and Mathematics in Toxicogenomics, With Special Reference to Data Interpretation and Oscillatory Dynamics Toxicol Pathol, January 1, 2004; 32(1_suppl): 13 - 25. [Abstract] [PDF]