Book of Abstracts: Albany 2007

category image Albany 2007
Conversation 15
June 19-23 2007

Protective Action of Theophylline on Cisplatin and Mitomycin C Induced Apoptosis in Human Peripheral Blood Lymphocytes

Theophylline, a dietary plant compound is a phosphodiesterase inhibitor, and used often in the treatment of asthma. This methyl substituted xanthine is recognized as an immunomodulator affecting T-lymphocytes both in vitro and in vivo (1). Theophylline is known to bind with nucleic acids and inhibit the DNA intercalation due to ethidium bromide or acridine orange upon intercalation into nuclear DNA (2). It has been of our interest to evaluate the antimutagenic/anticarcinogenic potential of this compound, thereby protecting normal cells from genotoxicity. The present study aims to determine the protective role of theophylline (200 µM) against the apoptosis induced by cytotoxic agents such as cisplatin and mitomycin C has been analysed in peripheral blood human lymphocytes. Loss of plasma membrane phospholipid asymmetry and DNA fragmentation and morphological changes in lymphocytes is studied using fluorescence microscopy, transmission electron microscopy, gel electrophoresis, and flow cytometric techniques. Significant changes in the morphology of lymphocytes associated with fragmentation of nuclei and DNA fragmentation is observed, when they are exposed to cisplatin and mitomycin C, but this is found to be considerably reduced upon treatment of theophylline. This is suggestive of the protective role of theophylline against the apoptosis induced by these DNA damaging agents and hence highlights the therapeutic significance of theophylline in modulating cellular processes.

References and Footnotes
  1. Ward, A. J., McKenniff, M., Evans, J. M., Page, C. P., and Costello, J. F. Am Rev Respir Dis. 147, 518-23, (1993).
  2. Maria Johnson, I., Bhuvan Kumar, S. G., and Malathi, R. J. Biomol. Strut. Dyn. 20, 677-686, (2003).

S. Usha
I. Maria Johnson1
R. Malathi

University of Madras
Chennai 600113 India
1Dept of Medicine
Univ. of Tennessee
Health Science Center
874 Union Avenue
Memphis TN 38163