20th-banner-rev.png

Albany 2019: 20th Conversation - Abstracts

category image Albany 2019
Conversation 20
June 11-15 2019
Adenine Press (2019)

The Influence of Hydrocortizone and Cisplatin Co-Administration to Rats on Chromatin Olygonucleosomal Fragmentation in Liver Nuclei

Accumulation of cisplatin in normal tissues in the course of treatment of cancer patients is responsible for severe adverse effects. Thus, curative effect of cisplatin is attenuated due to dose-limiting toxicity and growing resistance of cancer cells to the drug. To prevent cisplatin-induced side effects e.g. inflammation, nausea and vomiting, hydrocortisone is commonly co-administrated with cisplatin. Cells that undergo cytotoxic insults committed life or die decisions depending on genetic programs, which could be triggered by modulation of chromatin condensation. From the other hand, it is widely recognized that biological activities of hydrocortisone are mediated by hormone receptors, which bind and locally modify chromatin structure. However, little is known about possible effect of co-treatment with cisplatin and hydrocortisone on chromatin structure. To study whether DNA-binding of hydrocortisone receptors can interfere with DNA-cisplatin adducts and alter chromatin structure, we employed chromatin structure-dependent assay, using artificially activated intra-nuclear apoptotic Mg+2 and Ca+2 /Mg+2 -dependent endonucleases [1,2] and DNase 1 accessibility test. Our data come to show, that co-administration of cisplatin and hydrocortisone to rats modulated liver chromatin DNase 1 accessibility in time-dependent manner. Elevated resistance to DNase 1 in 4 h after treatment of rats with hydrocortisone and cisplatin coincided with the rise of liver DNA Tm, and was accompanied by descending intensity of DNA internucleosomal fragmentation. This data prompt that hydrocortisone–cisplatin interaction could prevent loosening of chromatin in internucleosomal chromatin regions induced by cisplatin treatment and, thus, might modulate its pharmacological outcomes.

References

    1. P. Widlak, L. Peng, X. Wang, W. T. Garrard. (2000). Cleavage Preferences of the Apoptotic Endonuclease DFF40 (Caspase-activated DNase or Nuclease) on Naked DNA and Chromatin Substrates. The Journal Of Biological Chemistry 275, 11(17), 8226–8232.

    2. D. Matassov, T. Kagan, J. Leblanc, M. Sikorska, Z. Zakeri. (2004). Measurement of apoptosis by DNA fragmentation. Methods Mol Biol 282, 1-17.

Anush Asatryan
Irina Artsruni
Karine Matinyan
Emil Gevorgyan

Department of Biophysics
Yerevan State University
Yerevan, Armenia, 0025

Ph: (374)91180810
Email: anush.asatryan@ysu.am