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

Home/Archive/PubMed

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

View original source ↗Export metadata ↓

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.

Explore related subjects

Amnion Carcinogens Cells, Cultured DNA Damage Humans Methylnitronitrosoguanidine Mutagenicity Tests NAD Poly(ADP-ribose) Polymerases Journal Article

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

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/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Parturition.

Explore the source record for details and available documents.

Amnion↗

PubMed2007

Intrathoracic pressure in congenital chylothorax: keystone for the rationale of thoracoamniotic shunting?

Thoracoamniotic shunting in fetal pleural effusion has poor results, with an overall survival of less than 50% when hydrops is associated. Those cases without hydrops presented the best evolution, but the indication in these cases remains controversial. We present a dichorionic diamniotic twin pregnancy at 29 weeks' with right pleural effusion and hydrops, in which one fetus presented diaphragm inversion and mediastinal shift, both considered as ultrasonographic signs of thoracic hypertension. A thoracoamniotic shunt reversed these signs immediately. Nevertheless, 1 week after, these signs and skin edema reappeared and the effusion increased, leading to a second thoracocenthesis for drainage and intrathoracic pressure measurement. Amniotic fluid and intrathoracic pressures were found at 21 and 39 mm Hg, respectively. A cesarean section was performed and the catheter was found to be obliterated by cellular detritus of leukocytes and fibrin. Our conclusion is that ultrasonographic signs of elevated thoracic pressure are a keystone for the shunt indication, and that this could be corroborated by direct measurements. This can be an important parameter for precise indication of thoracoamniotic shunting.

Amnion↗

PubMed2007

Rate of epithelialisation and re-operations in corneal ulcers treated with amniotic membrane transplantation combined with botulinum toxin-induced ptosis.

OBJECTIVE: To examine the efficacy of amniotic membrane transplantation (AMT) and/or botulinum toxin type A-induced ptosis (Dysport) in the treatment of corneal ulcerations of different entities. METHODS: Retrospective evaluation of 137 cases of corneal ulcers which have been treated with AMT, botulinum toxin type A and perforating keratoplasty (pKP). Regarding corneal ulcerations the patients were divided into three groups: group A, patients initially having received an AMT (92 eyes eventually followed by AMT or pKP as a second intervention); group B, patients initially having received an AMT (32 eyes followed by botulinum toxin type A injection in the upper lid as a second intervention); group C, patients initially treated only by botulinum toxin type A injection (13 eyes followed occasionally by AMT or pKP or additional botulinum toxin type A injection). Additionally, we analysed the complete epithelialisation rate of the ocular surface in respect to different ocular and systemic diseases and compared the frequency of re-operations in each group. RESULTS: The overall follow-up was 14.2 (+/-14.7 months; range from 1 to 60 months). The total frequency of re-operations was 45.3% (overall time until complete epithelialisation 12.7 (+/-6.1) days). If the patient was initially treated with an AMT (group A), the re-operation rate was 44.6%. Treating affected eyes in this group with a subsequent amniotic membrane resulted in a reduction of re-operation rate to 30.4%. In cases with induced ptosis by injecting botulinum toxin type A in the M. levator palpebrae (group B), the re-operation frequency could be reduced to 34.4% with similar times of epithelialisation [group A: 12.0 (+/-6.5) days and group B: 11.7 (+/-5.5) days]. In group C, with botulinum toxin type A alone initially, the re-operation rate of 69.2% was the highest one compared with groups A and B; this rate could be drastically reduced by a following AMT to 23.1%. Surprisingly, in the few successful cases with botulinum toxin type A alone a quite low epithelialisation time of 6.5 (+/-1.3) days was achieved, but turned out to be similar after additional interventions if compared with the other groups (botulinum toxin type A + AMT: 15.7 (+/-4.9) day). CONCLUSION: AMT alone and combined with botulinum toxin type A-induced ptosis is an effective surgical approach for managing severe corneal ulcerations by promoting wound healing and stabilizing ocular surface homeostasis.

Amnion↗