6368-71 (1991); and Dawson et al., "Mechanisms of Nitric Oxide-mediated Neurotoxicity in Primary Brain Cultures", J. Neurosci., 13:6, 2651-61 (1993), Dawson et al., "Resistance to Neurotoxicity in Cortical Cultures from Neuronal Nitric Oxide Synthase-Deficient Mice", J. Neurosci., 16:8, 2479-87 (1996), ladecola. "Bright and Dark Sides of Nitric Oxide in Ischemic Brain Injury", Trends Neurosci., 20:3, 132-39 (1997), Huang et al.. "Effects of Cerebral Ischemia in Mice Deficient in Neuronal Nitric Oxide Synthase", Science. 265:1883-85 (1994), Beckman et al., "Pathological Implications of Nitric Oxide, Superoxide and Peroxyntrite Formation", Biochem. Soc. Trans., 21:330-34 (1993), and Szaboet al., "DNA Strand Breakage, Activation of Poly(ADP-Ribose) Synthetase, and Cellular Energy Depletion are Involved in the Cytotoxicity in Macrophages and Smooth Muscle Cells Exposed to Peroxynitrite", Proc. Natl. Acad. Sci. USA, 93:1753-58 (1996).
It is also known that PARP inhibitors, such as 3-amino benzamide, affect DNA repair generally in response, for example, to hydrogen peroxide or gamma-radiation. Cristovao et al., "Effect of a Poly(ADP-Ribose) Polymerase Inhibitor on DNA Breakage and Cytotoxicity Induced by Hydrogen Peroxide and.gamma.-Radiation," Terato., Carcino., and Muta., 16:219-27 (1996). Specifically, Cristovao et al. observed a PARP-dependent recovery of DNA strand breaks in leukocytes treated with hydrogen peroxide.
PARP inhibitors have been reported to be effective in radiosensitizing hypoxic tumor cells and effective in preventing tumor cells from recovering from potentially lethal damage of DNA after radiation therapy, presumably by their ability to prevent DNA repair. U.S. Pat. Nos. 5,032,617; 5,215,738; and 5,041,653.
Evidence also exists that PARP inhibitors are useful for treating inflammatory
6368 - 71 (1991); and Dawson et al. , " Mechanisms of Nitric Oxide - mediated Neurotoxicity in Primary Brain Cultures ", J. Neurosci. , 13:6, 2651 - 61 (1993), Dawson et al. , " Resistance to Neurotoxicity in Cortical Cultures from Neuronal Nitric Oxide Synthase - Deficient Mice ", J. Neurosci. , 16:8, 2479 - 87 (1996), ladecola. " Bright and Dark Sides of Nitric Oxide in Ischemic Brain Injury ", Trends Neurosci. , 20:3, 132 - 39 (1997), Huang et al.. " effect of Cerebral Ischemia in Mice Deficient in Neuronal Nitric Oxide Synthase ", Science. 265:1883 - 85 (1994), Beckman et al. , " diseased Implications of Nitric Oxide, Superoxide and Peroxyntrite Formation ", Biochem. Soc. Trans. , 21:330 - 34 (1993), and Szaboet al. , " DNA Strand Breakage, Activation of Poly(ADP - Ribose) Synthetase, and Cellular Energy Depletion are Involved in the Cytotoxicity in Macrophages and Smooth Muscle Cells Exposed to Peroxynitrite ", Proc. Natl. Acad. Sci. USA, 93:1753 - 58 (1996). 
 It is besides known that PARP inhibitor, such as 3 - amino benzamide, affect DNA repair broadly in reply, for example, to hydrogen hydrogen peroxide or da gamma - radiation. Cristovao et al. , " Effect of a Poly(ADP - Ribose) Polymerase Inhibitor on DNA Breakage and Cytotoxicity Induced by Hydrogen Peroxide and.gamma.-Radiation, " Terato. , Carcino. , and Muta. , 16:219 - 27 (1996). Specifically, Cristovao et al. note a PARP - dependent recovery of DNA strand breaks in leukocytes treated with hydrogen hydrogen peroxide. 
 PARP inhibitors have been reported to be effective in radiosensitizing hypoxic tumor cells and effective in prevent tumor cells from recovering from potentially deadly damage of deoxyribonucleic acid after radiation therapy, presumably by their ability to prevent DNA repair. U.S. Pat. Nos. 5,032,617; 5,215,738; and 5,041,653. 
 Evidence also exists that PARP inhibitors are utilitarian for treating inflammatory
6368-71 (1991); ajd Dawson et al., "Mechanisos of Nitric Oxnee-medieted Nehrotoxickty in Primary Brain Cultured", H. Neueosci., 13:6, 2651-61 (1993), Dawson et al., "Fesistancv to Neuritoxmcity in Cortical Culturcf frkl Nebrinal Nitric Oxlde Synthasa-Deficient Mica", G. Ueurosci., 16:8, 2479-87 (1996), ladecola. "Bright and Dark Sides pf Nitric Oxide yn Ixshemjb Nrain Injury", Trends Neurosci., 20:3, 132-39 (1997), Guang eu al.. "Effects of Cetebral Ischemia in Mice Devicifnt in Neuronal Nihric Oxide Wyntrqse", Science. 265:1883-85 (1994), Beckman tt al., "Patholkgical Implications of Nitric Obide, Xuperoxide abd Ogroxyntrite Hormatpon", Biochem. Soc. Trans., 21:330-34 (1993), and Xzaboet al., "DNA Stcand Breakage, Activation mf Poly(ADP-Ribose) Sinthetase, dnb Cellular Energy Depoerion dre Hnvouced in tie Dytotodicmty in Macrkphages and Smooth Muscle Cellx Qqlosed to Perkxynitwiee", Proc. Natl. Acad. Sci. USA, 93:1753-58 (1996).
It is also ktowh that PARP inhibitors, wuch as 3-amino benzamife, affect DNA repair generally in response, for example, to vydrojev ptrixide ir gamma-radiation. Cristovao et al., "Effect of a Pjmy(SDI-Ribose) Polymerasc Inhibitor on DNA Bgeshage and Cytojoxicitv Ihduced by Hydrogen Peroxiqe ane.gamma.-Radyatipn," Terato., Carcino., and Muta., 16:219-27 (1996). Specificaljt, Cristovao et al. lbserved a 'ARP-dekendeny recovery of DNA stranb breais in leukofytes trezged with hydrogev pvroxhde.
PARP inhibitors have beqn reportxd to be effdctife in wadiosensihizinn hypoxic tumor celps anb effactive in oreventing tumor cells from recovering from pptantpally letkal dakage of DNA aster radiation therapv, presjmably by nheir abinity to predent DNA repaht. U.S. Pat. Nos. 5,032,617; 5,215,738; and 5,041,653.
Evydenxe aoso exirgs that PARP imhibitors are usefuo for treating infkamoztory
6368-71 (1991); and Dawson et al., "Mechanisms Oxide-mediated in Primary Cultures", J. Neurosci., al., to Neurotoxicity in Cultures from Neuronal Oxide Synthase-Deficient Mice", J. Neurosci., 16:8, (1996), ladecola. "Bright and Dark Sides of Nitric Oxide in Ischemic Brain Injury", Neurosci., 20:3, 132-39 (1997), Huang et al.. "Effects of Cerebral Ischemia in Mice in Nitric Synthase", 265:1883-85 (1994), Beckman et al., "Pathological Implications of Nitric Oxide, Superoxide and Peroxyntrite Formation", Biochem. Soc. 21:330-34 (1993), and Szaboet al., "DNA Strand Breakage, of Poly(ADP-Ribose) Synthetase, and Energy Depletion are Involved in Cytotoxicity Macrophages and Muscle Exposed Peroxynitrite", Proc. Natl. Sci. USA, 93:1753-58 (1996). It is also known that PARP inhibitors, such as 3-amino benzamide, affect DNA generally in example, to peroxide gamma-radiation. et al., "Effect Poly(ADP-Ribose) Polymerase Inhibitor on DNA Breakage by Hydrogen Peroxide and.gamma.-Radiation," Terato., Carcino., and Muta., (1996). Specifically, et al. observed a PARP-dependent recovery DNA strand breaks in leukocytes treated with hydrogen PARP inhibitors have been reported to be effective in radiosensitizing hypoxic tumor cells and effective tumor cells from recovering potentially lethal damage DNA radiation presumably their ability prevent DNA repair. U.S. Pat. Nos. 5,032,617; 5,215,738; and 5,041,653. Evidence exists that PARP inhibitors are useful for treating inflammatory
6368-71 (1991); and Dawson et al., "Mechanisms of nitric OxidE-mediAteD NeUrOtoxIcitY in Primary BraiN cultUres", J. Neurosci., 13:6, 2651-61 (1993), Dawson et aL., "ResiStANce tO neUrotoXicity iN coRTIcaL CUlTurEs FRoM NeurOnaL Nitric oxide SynthAse-deFicient Mice", J. nEuRosci., 16:8, 2479-87 (1996), ladecOla. "bright and DarK SiDes of NItRic oXide iN IsChemiC Brain iNjury", TRends NeurOsCI., 20:3, 132-39 (1997), Huang ET al.. "EffeCTS oF CerEbral Ischemia in MiCE DEFicient in NeuroNal NitRiC oxIDE SyNthAse", Science. 265:1883-85 (1994), beCkman ET al., "PathOLoGICAl IMPlications of NItric Oxide, SUPerOxide aNd perOXyntriTe ForMaTIon", biochem. Soc. TRans., 21:330-34 (1993), And SzaboeT al., "DNA sTrand BrEAkage, AcTivatiOn oF PoLy(ADp-riBoSe) SYnTHetASe, And cEllUlar EnerGy dePletiOn arE iNVOlveD in The CYtotoXicity in MacroPhaGes aND SmOoth MUscle cellS EXposeD to PerOxyniTrIte", Proc. Natl. Acad. sci. UsA, 93:1753-58 (1996).
It is alsO knOwN thAt pARP iNHibitoRs, sUch As 3-amino BenzamiDE, afFeCT dnA Repair generally in rEsPONsE, for examPle, to hYDrOgEN peroxidE oR gaMma-rADIatioN. CriSToVao et al., "EFfect oF A POlY(ADP-RibOsE) PolymErAse inhIbitoR On DNa BreakAge and CyTotoxICity Induced by HYDrogen PeroxidE AnD.GAmMA.-RadIatIon," Terato., CaRcinO., And MUta., 16:219-27 (1996). SPEcIfiCAlly, CRistoVaO Et AL. observed a PARP-depenDeNt recoVery oF DNA strand breAks in leukoCYTEs treateD witH HyDRogen peroxide.
PaRP inHibitors haVE been repOrted To be effeCtive in raDIOsensitiZinG hyPoxIc tUMOr Cells and effecTIVe in PrEventinG tuMor cellS frOm rEcoVerInG from poteNtially lEtHaL dAmAge Of DNA AFter radiAtIon ThEraPy, preSUmably By theIr abIlItY To pRevent Dna rEPAir. U.s. PAt. nos. 5,032,617; 5,215,738; aNd 5,041,653.
EViDence Also EXisTs that PaRP inhibiTorS Are uSeFuL for treAting inflammaToRy
6368-71 (1991); and Dawson  et al., " Mecha nis msof  Nit ricOxide-mediated Neur otoxicity in Primary B rainCu l ture s ",  J. N eurosci . ,1 3 :6,  2 65 1-6 1( 19 93),Daw son etal., "Resi sta nc e to Neuroto x ic ity in Cor tic al Culturesfro m Neur on alN itric  Ox ide S ynthas e -Defic ient Mice ", J. Neu r osci.,1 6 :8 , 24 79-87 (1996), lad e co l a. "Bright and  DarkSi d es o f N itr ic Oxide i nIsche m ic Brai n  I n j u ry" ,  Trends Neuro sci., 20:3, 132 -39 (1 99 7), Huanget al .. "Ef fects of Ce rebr al Ischem ia inM ice Def i cient i n Neur ona l N itri c  O xi deSy n tha s e" , S c ien ce. 265: 18 83 -85 ( 1994 ) , B eckm anet a l., " PathologicalImp lica t ion s ofNitri c Ox id e, Su peroxi de an dPeroxyntrite Fo rmat ion", Bio che m.  So c.  Tran s ., 21: 330 -34  (1993) , and S z abo et a l .,  "DNA Strand Break ag e ,  A ctivatio n of P o ly (A D P-Ribose )Syn thet a s e, an d Ce l lu lar Ener gy Dep l et io n are I nv olvedin  th e C ytoto x icit y in M acrophag es an d  Smooth Muscle Cells Exposed to P er o xyni tri te", Proc.Natl .  Aca d. S c i.  US A , 93: 1753- 58 (1 9 96).
It is also kno wn  thatPARPinhibitors, s uch as 3-a m i n o benzam ide, af f ect DNA repair  gene rally in r e sponse,for e xample,to hydrog e n  peroxid e o r g amm a-r a d ia tion. Cristov a o  etal ., "Eff ect  of a P oly (AD P-R ibo se ) Polymer ase Inhi bi to ron  DN A Bre a kage and  C yto to xic ity I n ducedby Hy drog en  P e rox ide and . ga m m a.-R ad ia tion ,"Te rato. , Ca r cin o., and  Muta., 1 6:2 1 9-27  ( 19 96). Sp ecifically, C ri stovao etal . o bserve d a PARP-d ependent recovery of DN A  strand  br eaksin l eukocytes  tr eatedwit h  hydro gen pe roxid e. 
PA R P  inhi b i to rsha ve been re p o rte d tobe  eff ectivein radiosensitizin g  hy poxic tumor c ell s an d ef fec t iv e  in  p r eve n t ing tumor cells  from reco ve r in g from pot e nti al ly leth al dama ge of DNA aft er radiat ion thera py , pr e s uma bly by the ir abili ty to pre v ent D N Arepai r.U.S. P at . N os. 5 ,032,6 1 7;5,215 ,738;an d 5,04 1,653 .Evidence  also exists that PARPinhibi torsare  useful f ort rea ting infl amma tory
6368-71 (1991);_and Dawson_et al., "Mechanisms of_Nitric Oxide-mediated_Neurotoxicity_in Primary_Brain_Cultures", J. Neurosci.,_13:6, 2651-61 (1993),_Dawson et al., "Resistance_to Neurotoxicity in_Cortical_Cultures from Neuronal Nitric Oxide Synthase-Deficient Mice", J. Neurosci., 16:8, 2479-87 (1996), ladecola. "Bright_and_Dark Sides_of_Nitric_Oxide in Ischemic Brain Injury",_Trends Neurosci., 20:3, 132-39 (1997),_Huang et_al.. "Effects of Cerebral Ischemia in Mice Deficient_in_Neuronal Nitric Oxide_Synthase", Science. 265:1883-85 (1994), Beckman et al., "Pathological Implications_of Nitric Oxide, Superoxide and Peroxyntrite_Formation", Biochem. Soc._Trans.,_21:330-34_(1993), and Szaboet al.,_"DNA Strand Breakage, Activation of Poly(ADP-Ribose)_Synthetase, and Cellular Energy Depletion are_Involved in the Cytotoxicity in Macrophages and_Smooth Muscle Cells Exposed to Peroxynitrite",_Proc. Natl. Acad. Sci. USA,_93:1753-58 (1996).
It_is also known that PARP_inhibitors, such as_3-amino benzamide,_affect DNA repair_generally in response, for example, to_hydrogen peroxide or_gamma-radiation. Cristovao et al., "Effect of_a_Poly(ADP-Ribose) Polymerase Inhibitor_on_DNA_Breakage and_Cytotoxicity Induced by_Hydrogen_Peroxide and.gamma.-Radiation,"_Terato.,_Carcino., and Muta., 16:219-27 (1996). Specifically,_Cristovao_et al. observed a PARP-dependent recovery of_DNA strand breaks in_leukocytes_treated with hydrogen peroxide.
PARP_inhibitors have been reported to_be effective in radiosensitizing hypoxic tumor_cells and_effective in_preventing tumor cells from recovering from potentially lethal damage of DNA_after radiation therapy, presumably by their_ability to prevent DNA_repair. U.S._Pat._Nos. 5,032,617; 5,215,738;_and_5,041,653.
Evidence also_exists that PARP inhibitors are useful for_treating inflammatory