Assessment of DNA damage in spleen, bone marrow, and peripheral blood from malnourished rats by single cell gel electrophoresis assay

Abstract

Severe malnutrition is widely distributed throughout the world and exhibits a high prevalence in developing countries. Experimental malnutrition models have been useful to study the effects of malnutrition at early ages. The purpose of this study was to determine if severe malnutrition induced during lactation in rats increases DNA damage in spleen, peripheral blood, and bone marrow cells, as well as in isolated lymphocytes or lymphoid cells from the same tissues. These cells were obtained from malnourished rats at weaning (21 days of age). DNA damage was estimated by using the alkaline single cell electrophoresis assay. The results obtained in this study indicate that malnutrition is associated with a significant increase in DNA damage in all cell types that were studied in malnourished rats. The analysis of the length of DNA migration and dispersion coefficient showed that some cell types were more susceptible to DNA damage related with malnutrition. The damage observed could be due to the deficiency of several essential nutrients required for protein synthesis that are associated with DNA integrity, impaired DNA repair mechanisms, and/or to the unavailability of molecules necessary to protect the cells against DNA oxidative damage. This damage may produce negative effects for the further development of the organism, since bone marrow is the main site of hematopoiesis and spleen is an important lymphopoietic organ. Also, the increased level of DNA damage in peripheral blood lymphocytes and leukocytes could be related to negative effects such as a deficient immune response.

Protein-energy malnutrition halts hemopoietic progenitor cells in the G0/G1 cell cycle stage, thereby altering cell production rates

“…It has been reported that the proliferative capacity of bone marrow and the spleen is hindered in malnourished mice and that there is a reduction in the number of pluripotent cells and an increase in the time taken for a single cell cycle to be completed (13). Malnutrition reduces the number of granulo-monocytic colony forming units (14) and leads to DNA damage (15) and to cytogenetic alterations (16). The exact mechanisms underlying these findings are not clear.…”

Genomic lesions and colorectal carcinogenesis: the effects of protein-calorie restriction and inulin supplementation on deficiency statuses

“…The relationship between malnutrition and DNA damage, which includes effects on chromosomal aberrations (Alu and Murthy, 1993) and increased frequencies of sister chromatid exchange (Betancourt et al, 1986), micronuclei , and comets (Cortés et al, 2001), has been previously reported. However, other studies have reported no correlations between malnutrition and increased genetic damage, whether genotoxic and/or mutagenic (Betancourt et al, 1995;Celik et al, 2012).…”

“…The following can be inferred to explain the increased genotoxicity observed in this experiment: I) the lack of nutrients causes the inadequate synthesis of proteins involved in the cell cycle and maintenance of DNA integrity and DNA repair; II) cells in malnourished bodies cannot sustain baseline DNA damage repair mechanisms; and III) malnutrition causes a lack of enzymes that prevent oxidative processes and free radical production (Webster et al, 1996;Cortés et al, 2001).…”

“…Studies have also reported that protein-calorie restriction decreases the activities of glutathione peroxidase, the antioxidant enzyme glutathione reductase, and glucose-6-phos-phate dehydrogenase in addition to reducing the serum levels of the important antioxidants vitamin E and glutathione (Cortés et al, 2001).…”

Recognition memory and DNA damage in undernourished young rats

“…There is evidence indicating that the reduction in the basal metabolic rate, which would be caused by the decreased rate of cellular oxygen consumption (Masoro 2000), mitigates DNA damage arising from oxidative stress (Celik et al 2012). In animals, a significant increase in DNA damage has been reported to be associated with the undernourished state (Cortés et al 2001). However, the mechanisms involved in the relationship between undernutrition, CR and cell damage are not fully understood, particularly in cells of the central nervous system, such as hippocampal cells.…”