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PubMed · 2115165

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.

Y Yu·Y Dai·M Fang·X Chen
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Abstract

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.

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AmnionCarcinogensCells, CulturedDNA DamageHumansMethylnitronitrosoguanidineMutagenicity TestsNADPoly(ADP-ribose) PolymerasesJournal Article

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Y Yu, Y Dai, M Fang, X Chen. 1990. 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.. https://pubmed.ncbi.nlm.nih.gov/2115165/

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