Skip to main content
Log in

In Vivo Exposure of Swiss Albino Mice to Chronic Low Dose of Dimethylnitrosamine (DMN) Lowers Poly-ADP-Ribosylation (PAR) of Bone Marrow Cell and Blood Lymphocyte Proteins

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Efforts to identify an easy and convenient biomarker of carcinogenesis with potentials of application in mass screening program continue. In a series of investigations on mice exposed to different carcinogens, poly-ADP-ribosylation (PAR) of cellular proteins of different tissues has been shown to be a potential biomarker of carcinogenesis. Because blood based biomarker of carcinogenesis offers significant advantage in its use in a cancer screening program, this investigation was undertaken to find correlations between initiation of carcinogenesis and PAR of bone marrow cell (BMC) and blood lymphocyte (BL) proteins in mice chronically exposed to low dose of dimethylnitrosamine (DMN) for up to four weeks in vivo. The exposure was either alone or in combination with 3-aminobenzamide (3-AB), an inhibitor of PAR. Total PAR of cellular proteins and of histone H1 protein were monitored by slot and Western blot immunoprobe assays, respectively. The PAR of total cellular proteins as well as of histone H1 was down-regulated in duration of exposure dependent manners. The results suggest that BMC and BL mirrored status of PAR in other tissues. This finding opens up the possibility of using PAR as a biomarker of carcinogenesis in a blood based test utilizing immunoprobe assay of cellular PAR.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

3-AB:

3-aminobenzamide

BCIP/NBT:

5-bromo-4-chloro-3-indolyl phosphate-nitro blue tetrazolium

BL:

blood lymphocytes

BMC:

bone marrow cells

DMN:

dimethylnitrosamine

H1:

histone H1

NAD:

nicotinamide adenine dinucleotide

PAb:

polyclonal antibodies

PAR:

poly-ADP-ribosylation

PARP:

poly-ADP-ribose polymerase

PVDF:

poly-vinyl dinitrofluoride

WH:

whole homogenate

References

  1. Althaus FR, Richter C: Poly (ADP-ribose) biosynthesis. In: Solioz M (ed). ADP-Ribosylation of Proteins -- Enzymology and Biological Significance: Molecular Biology, Biochemistry and Biophysics. Springer-Verlag, New York, 1987, pp 1–230

    Google Scholar 

  2. Boulikas T: Poly (ADP-ribosylation), DNA strand breaks, chromatin and cancer. Toxicological Letters 67: 129–150, 1993

    Article  CAS  Google Scholar 

  3. Miwa M, Sugimura T: ADP-ribosylation and carcinogenesis. In: Moss J and Vaughan M (eds). ADP-ribosylating Toxins and G-proteins: Insights into signal transduction. American Society for Microbiology, Washington DC, 1990, pp 543–560

    Google Scholar 

  4. Pariat T, Sharan RN: Qualitative change in mice liver HMG proteins after low dose chronic administration of aqueous extract of betel nut and diethylnitrosamine. Hepatology Research 12: 177–185, 1998

    Article  Google Scholar 

  5. Saikia JR, Schneeweiss FHA, Sharan RN: Arecoline induced changes of poly-ADP-ribosylation of cellular proteins and its influence on chromatin organization. Cancer Letters 139: 59–65, 1999

    Article  PubMed  CAS  Google Scholar 

  6. Pariat T, Sharan RN: Role of mouse spleen cell HMG proteins and their poly ADP-ribosylation in betel nut induced carcinogenesis. Indian Journal of Biochemistry and Biophysics 39: 130–135, 2002

    CAS  Google Scholar 

  7. Kma L, Sharan RN: Negative correlation between poly-ADP-ribosylation of mouse blood lymphocytes proteins and dimethylnitrosamine induced initiation of carcinogenesis as revealed by Slot- and Western blot immunoassays. Proceedings of the National Academy of Sciences, India 73B: 43–51, 2003

    Google Scholar 

  8. Devi BJ, Schneeweiss FHA, Sharan RN: Negative correlation between poly-ADP-ribosylation of spleen cell histone proteins and initial duration of dimethylnitrosamine exposure to mice in vivo measured by Western blot immunoprobe assay: a possible biomarker for cancer detection. Cancer Detection and Prevention 29: 66–71, 2005

    Article  PubMed  CAS  Google Scholar 

  9. Devi BJ, Sharan RN: Progressive reduction in poly-ADP-ribosylation of histone proteins during Dalton's lymphoma induced ascites tumorigenesis in mice. Cancer Letters (in press), 2005 doi:10.1016/j.canlet.2005.07.014.

  10. Sharan RN, Devi BJ, Humtsoe JO, Sailkia JR, Kma L Detection and quantification of poly-ADP-ribosylated cellular proteins of spleen and liver tissues of mice in vivo by slot and Western blot immunoprobing using polyclonal antibody against mouse ADP-ribose polymer. Molecular and Cellular Biochemistry 278: 213–221, 2005

    Article  PubMed  CAS  Google Scholar 

  11. Sharan RN, Devi BJ, Humtsoe JO, Schneeweiss FHA: Immunodetection of cellular poly-ADP-ribosylation. In: Sharan RN (ed). Trends in Radiation and Cancer Biology. Forschungszentrum Juelich GmbH, Germany, International Co-operation Bilateral Seminars Series volume 29, 1998, pp 240–243

  12. Sharan RN: Association of betel nut with carcinogenesis (review). The Cancer Journal 9: 13–19, 1986

    Google Scholar 

  13. Christine MI, Bernard BS: Inhibition of poly (ADP-ribose) synthesis may affect DNA repair prior to ligation. Carcinogenesis 8: 39–43, 1987

    PubMed  Google Scholar 

  14. Purnell MR, Whish WJD: Novel inhibitors of poly (ADP-ribose) synthetase. Biochemical Journal 185: 775–777, 1980

    PubMed  CAS  Google Scholar 

  15. Pariat T, Sharan RN: Low dose exposure of diethylnitrosamine affects mice liver thymidine kinase. Life Sciences 57: 2431–2437, 1995

    Article  PubMed  CAS  Google Scholar 

  16. Boyum A: Separation of leucocytes from blood and bone marrow. Scandinavian Journal of Clinical Laboratory Investigation 21: 77–89, 1968

    CAS  Google Scholar 

  17. Keller SE, Schleifer SJ, McKegney SJ, Camerino M, Stein M: A simplified method for assessing PHA-induced stimulation of rat peripheral blood lymphocytes. Journal of Immunological Methods 51: 287–291, 1982

    Article  PubMed  CAS  Google Scholar 

  18. Rosenberg IM: Antibody preparation. In: Protein Analysis and Purification, Benchtop Techniques, Birkhauser, 1996, pp 370–371

  19. Bradford MM: A rapid and sensitive method for quantification of microgram quantities of proteins using the principle of dye binding. Analytical Biochemistry 72: 248–254, 1976

    Article  PubMed  CAS  Google Scholar 

  20. Boulikas T: Poly (ADP-ribosylated) histones in chromatin replication. Journal of Biological Chemistry 265: 14638–14647, 1990

    PubMed  CAS  Google Scholar 

  21. Millar BC: Cell biology of cancer. In: Horwich A (ed). Oncology -- A Multidisciplinary Text Book. Chapman and Hall, London, 1995

    Google Scholar 

  22. Simbulan-Rosenthal CM, Rosenthal DS, Luo R, Li JH, Zhang J, Smulson ME: Inhibition of poly (ADP-ribose) polymerase activity is insufficient to induce tetraploidy. Nucleic Acids Research 29: 841–849, 2001

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to R. N. Sharan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kma, L., Sharan, R.N. In Vivo Exposure of Swiss Albino Mice to Chronic Low Dose of Dimethylnitrosamine (DMN) Lowers Poly-ADP-Ribosylation (PAR) of Bone Marrow Cell and Blood Lymphocyte Proteins. Mol Cell Biochem 288, 143–149 (2006). https://doi.org/10.1007/s11010-006-9130-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-006-9130-x

Keywords

Navigation