ADPRT-MEDIATED DECREASE OF CELLULAR NAD CONTENT AND THE DETECTION OF CHEMICALLY INDUCED DNA DAMAGE DEVELOPMENT OF A NEW SHORT-TERM SCREENING TEST FOR MUTAGENS

It was found that the DNA-damaging agents N-methyl-N’-nitro-N-nitrosoguanidine(MNNG),methyl-methanesulphonate(MMS)and 4-nitroquinoline-N-oxide(4NQO)could stimulate ADP-ribosyl transferase(ADPRT)activity and reduce the cellular NAD content in a dose-dependent way.The reduction of NAD after DNA damage could be partially or completelyprevented by ADPRT inhibitors,3-aminobenzamide or nicotinamide,which showed noinfluence on reduction of NAD induced by metabolic blocking agents.Therefore,a simpleand specific method to detect DNA-damaging mutagens by measuring ADPRT-mediateddecrease of cellular NAD content was explored.Using β-naphthofiavone,a mixed functionoxygenase inducer,together with induced or uninduced human amnion FL cells,it was foundthat aflatoxin B1,benzo(a)pyrene,2-acetylaminofluorene,9,10-dimethylanthracene andethylcarbamate could induce the ADPRT-mediated decrease of cellular NAD content,while4-acetylaminofluorene,anthracene,isopropyl-N-(3-chlorophenyl)-carbamate,β-propiolactone,γ-butyrolactone,cyclophosphamide and safrol could not.The results indicate that this isa cheap and specific method to detect DNA damage caused by chemical carcinogens/mutagenswith a spccificity approaching that of the unscheduled DNA synthesis assay.