Dimethylnitrosamine-induced reduction in the level of poly-ADP-ribosylation of histone proteins of blood lymphocytes--a sensitive and reliable biomarker for early detection of cancer.

Lakhan Kma,Rajeshwar Nath Sharan

doi:10.7314/apjcp.2014.15.15.6429

Abstract

Poly-ADP-ribosylation (PAR) is a post-translational modification of mainly chromosomal proteins. It is known to be strongly involved in several molecular events, including nucleosome-remodelling and carcinogenesis. In this investigation, it was attempted to evaluate PAR level as a reliable biomarker for early detection of cancer in blood lymphocyte histones. PAR of isolated histone proteins was monitored in normal and dimethylnitrosamine (DMN)-exposed mice tissues using a novel ELISA-based immuno-probe assay developed in our laboratory. An inverse relationship was found between the level of PAR and period of DMN exposure in various histone proteins of blood lymphocytes and spleen cells. With the increase in the DMN exposure period, there was reduction in the PAR level of individual histones in both cases. It was also observed that the decrease in the level of PAR of histones resulted in progressive relaxation of genomic DNA, perhaps triggering activation of genes that are involved in initiation of transformation. The observed effect of carcinogen on the PAR of blood lymphocyte histones provided us with a handy tool for monitoring biochemical or physiological status of individuals exposed to carcinogens without obtaining biopsies of cancerous tissues, which involves several medical and ethical issues. Obtaining blood from any patient and separating blood lymphocytes are routine medical practices involving virtually no medical intervention, post-procedure medical care or trauma to a patient. Moreover, the immuno-probe assay is very simple, sensitive, reliable and cost-effective. Therefore, combined with the ease of preparation of blood lymphocytes and the simplicity of the technique, immuno-probe assay of PAR has the potential to be applied for mass screening of cancer. It appears to be a promising step in the ultimate goal of making cancer detection simple, sensitive and reliable in the near future.

Highlights

The fundamental objective of science is to make the human life qualitatively better, free of diseases and sufferings
The observed effect of carcinogen on the PAR of blood lymphocyte histones provided us with a handy tool for monitoring biochemical or physiological status of individuals exposed to carcinogens without obtaining biopsies of cancerous tissues, which involves several medical and ethical issues
Histone proteins were prepared from spleen cells (SC) and blood lymphocytes (BL) of normal and DMN treated mice

Summary

Introduction

The fundamental objective of science is to make the human life qualitatively better, free of diseases and sufferings. Even in the new millennium with all encompassing developments in science and technology related to medical field including publication of human genome sequence, the epoch making feat of human endeavors, cancer continues to be a most deadly disease threatening mankind today. It is to be noted that search for appropriate molecular and biochemical markers for early cancer diagnosis has great relevance to the present approach of our fight against cancer since by early diagnosis cancer mortality and morbidity are likely to reduce significantly (Khan et al, 2012; Luna et al, 2012; van der Bilt et al 2012; Bao et al, 2013; Hensing and Salgia, 2013; Suradej et al, 2013; Wang et al, 2013; Behrens et al, 2014; Sigari et al, 2014). It is to be noted that study of cancer cases by looking into the proteomics profiles of patients has yielded valuable clinical correlation between them (Yang et al, 2012; Marzinke et al, 2013; Soond et al, 2013; Taguchi and Hanash, 2013; Ueda et al, 2013; Alvarez-Chaver et al, 2014; Harbeck et al, 2014; Huang et al, 2014; Humphries et al, 2014; Kondo, 2014)

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Conclusion