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  

作　　者：余应年 戴一凡 方明 陈星若 

机构地区：[1]Zhejiang Branch,CAMS,Hangzhou [2]Genetic Institute,Fudan University,Shanghai [3]Zhejiang Medical University,Hangzhou.

出　　处：《Chinese Medical Sciences Journal》1990年第1期19-24,共6页中国医学科学杂志（英文版）

摘　　要：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.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 completely prevented by ADPRT inhibitors,3-aminobenzamide or nicotinamide,which showed no influence on reduction of NAD induced by metabolic blocking agents.Therefore,a simple and specific method to detect DNA-damaging mutagens by measuring ADPRT-mediated decrease of cellular NAD content was explored.Using β-naphthofiavone,a mixed function oxygenase inducer,together with induced or uninduced human amnion FL cells,it was found that aflatoxin B_1,benzo(a)pyrene,2-acetylaminofluorene,9,10-dimethylanthracene and ethylcarbamate could induce the ADPRT-mediated decrease of cellular NAD content,while 4-acetylaminofluorene,anthracene,isopropyl-N-(3-chlorophenyl)-carbamate,β-propiolactone, γ-butyrolactone,cyclophosphamide and safrol could not.The results indicate that this is a cheap and specific method to detect DNA damage caused by chemical carcinogens/mutagens with a spccificity approaching that of the unscheduled DNA synthesis assay.

关 键 词：ADP-ribosyl TRANSFERASE NAD CONTENT SHORT-TERM test MUTAGEN 

分 类 号：R[医药卫生]