THE KEY INVOLVEMENT OF POLY(ADP-RIBOSYL)ATION IN DEFENSE AGAINST TOXIC AGENTS: MOLECULAR BIOLOGY STUDIES (AFOSR-89-0053) June 1,1998 PRINCIPAL INVESTIGATOR: MARK E. SMULSON, Ph.D. PROFESSOR OF BIOCHEMISTRY DEPARTMENT OF BIOCHEMISTRY AND MOLECULAR BIOLOGY GEORGETOWN UNIVERSITY SCHOOL OF MEDICINE

The Air Force employs or generates a variety of materials, such as fuels, some of which may be potentially hazardous and could be released into the environment. Effective tools are required to predict and assess the fate of these agents in the ; environment. It is equally important, to understand the basic biological mechanisms of these agents. We have thus begun to assess whether these fuels kill cells via scheduled cell death. During the past granting period we have developed a rela[ tively simple, inexpensive, and easy-to-use diagnostic tool for detecting whether ( a cell's DNA has been damaged by fuels. We have also performed the initial basis ' for an understanding of a key enzyme (apopain) which is involved in the cleavage ; of poly(ADP) ribose polymerase (PARP) during apoptosis. We feel that both ; contributions have potential applications for the screening of the toxicity of ' newly developed fuels intended for U.S. military use.