Early ROS-mediated DNA damage and oxidative stress biomarkers in Monoclonal B Lymphocytosis

Cancer Lett. 2012 Apr 28;317(2):144-9. doi: 10.1016/j.canlet.2011.11.018. Epub 2011 Nov 22.

Abstract

Monoclonal B Lymphocytosis (MBL) is defined as asymptomatic monoclonal B-cell expansion characterised by a CLL-phenotype, but with less than 5×10(9)/l circulating cells. Reactive oxygen species (ROS)-mediated cell damage plays a critical role in the initiation of carcinogenesis as well as in malignant transformation. The goal of this study was to perform an analysis of the oxidative stress statuses of patients affected by MBL and chronic lymphocytic leukaemia (CLL). We examined peripheral blood and urine specimens from 29 patients with MBL, 55 with CLL and 31 healthy subjects. There was a significant increase in the occurrence of the mutagenic base 8-oxo-2'-deoxiguanosine (8-oxo-dG) in the lymphocytes and urine of MBL and CLL patients compared with controls. Significant differences were also observed in the levels of the lipid peroxidation product malondialdehyde (MDA) and in the oxidised/reduced glutathione (GSSG/GSH) ratio, although an increase in 8-isoprostane was not detected. Interestingly, the antioxidant catalase activity of circulating lymphocytes decreased in the patient groups. In conclusion, early oxidative stress exists in patients with MBL and CLL, causing damage to DNA and lipid structures. The higher levels of 8-oxo-dG in lymphocytes than in urine may be related to a decrease in the capacity of DNA repair systems. There were no differences in the oxidative statuses of the MBL and CLL patients, suggesting that oxidative injuries appear during a pre-leukaemic state of the disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Aged
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology
  • Biomarkers / metabolism*
  • Biomarkers / urine
  • Chromatography, High Pressure Liquid
  • DNA Damage*
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / metabolism
  • Deoxyguanosine / urine
  • Dinoprost / analogs & derivatives
  • Dinoprost / metabolism
  • Dinoprost / urine
  • Female
  • Glutathione / metabolism
  • Glutathione / urine
  • Glutathione Disulfide / metabolism
  • Glutathione Disulfide / urine
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics
  • Leukemia, Lymphocytic, Chronic, B-Cell / metabolism
  • Leukemia, Lymphocytic, Chronic, B-Cell / urine
  • Lymphocytosis / genetics
  • Lymphocytosis / metabolism*
  • Lymphocytosis / urine
  • Male
  • Malondialdehyde / metabolism
  • Malondialdehyde / urine
  • Middle Aged
  • Oxidative Stress
  • Reactive Oxygen Species / metabolism*
  • Time Factors

Substances

  • Biomarkers
  • Reactive Oxygen Species
  • 8-epi-prostaglandin F2alpha
  • Malondialdehyde
  • 8-Hydroxy-2'-Deoxyguanosine
  • Dinoprost
  • Deoxyguanosine
  • Glutathione
  • Glutathione Disulfide