US EPA

1618064 

Journal Article 

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 

Yu, Y; Dai, Y; Fang, M; Chen, X 

1990 

Chinese Academy of Medical Sciences and Peking Union Medical College. Proceedings - Zhongguo Yixue Kexueyuan, Zhongguo Xiehe Yike Daxue Xuebao
ISSN: 0258-8757 

5 

1 

19-24 

English 

2115165 

BCI:BCI199090017695 

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 beta-naphthoflavone, a mixed function oxygenase inducer, together with induced or uninduced human amnion FL cells, it was found that aflatoxin B1, 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, beta-propiolactone, gamma-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 specificity approaching that of the unscheduled DNA synthesis assay. 

Amnion; Carcinogens; Cells, Cultured; DNA Damage; Methylnitronitrosoguanidine; Mutagenicity Tests; Poly(ADP-ribose) Polymerases; mutagenic agent; nicotinamide adenine dinucleotide; article; cell line; screening test