title: Aneuploidy assessed by DNA index influences the effect of iron status on plasma and/or supernatant cytokine levels and progression of cells through the cell cycle in a mouse model.
abstract: Aneuploidy, a condition associated with altered chromosome number, hence DNA index, is frequently seen in many diseases including cancers and affects immunity. Iron, an essential nutrient for humans, modulates the immune function and the proliferation of normal and cancer cells. To determine whether impaired immunity seen in iron-deficient subjects may be related to aneuploidy, we measured spleen cell DNA index, percent of cells in different phases of the cell cycle, plasma and/or supernatant IL-2, IL-10, IL-12, and interferon-gamma in control, pair-fed, iron-deficient, and iron-replete mice (N=20-22/group). The test and control diets differed only in iron content (0.09mmol/kg versus 0.9mmol/kg) and were fed for 68days. Mean levels of hemoglobin and liver iron stores of iron-deficient and iron-replete mice were 40-60% lower than those of control and pair-fed mice (P<0.05). Mean plasma levels of IL-10, interferon-gamma and percent of cells in S+G2/M phases were lower in mice with than in those without aneuploidy (P<0.05). Lowest plasma IL-12 and interferon-gamma concentrations were observed in iron-deficient mice with aneuploidy. Mean percents of cultures with aneuploidy and DNA indexes were higher in iron-deficient and iron-replete than in control and pair-fed mice likely due to delayed cell division (P<0.05). Aneuploidy decreased the concentration of IL-2 and interferon-gamma in baseline cultures while it increased that of interferon-gamma in anti-CD3 treated cultures. Aneuploidic indexes negatively correlated with cytokine levels, percents of cells in S+G2/M phases and indicators of iron status (P<0.05). Although chromosome cytogenetics was not performed, for the first time, we report that increased aneuploidy rate may modulate the immune function during iron-deficiency.
authors.affiliation: Louisiana State University Health Sciences Center, Department of Pediatrics, The Research Institute for Children's Hospital, USA. Electronic address: solokuv@msn.com.
authors.forename: Solo
authors.initials: S
authors.lastname: Kuvibidila
authors.affiliation: Department of Pulmonary Medicine,1542 Tulane Avenue, New Orleans, LA 70112, USA.
authors.forename: Connie
authors.initials: C
authors.lastname: Porretta
authors.affiliation: University of South Alabama College of Medicine, Department of Pediatrics, 2451 Fillingim St., Mobile, AL 36617, USA.
authors.forename: Surendra
authors.initials: S
authors.lastname: Baliga
mesh_terms: D000782:Aneuploidy; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood*; D004247:DNA / Q000378:metabolism*; D004032:Diet; D005260:Female; D007501:Iron / Q000378:metabolism*; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008934:Mitogens / Q000494:pharmacology; D023421:Models, Animal; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism
chemical_list: D016207:Cytokines; D008934:Mitogens; D004247:DNA; D007501:Iron
keywords: Aneuploidy; C; Con A; Cytokines; DNA synthesis phase; Fig; G(2)–M; G(o)–G(1); ID; IFN-γ; IL; Iron deficiency; Lymphocyte proliferation; Mitogens; NBSC; PF; S; anti-CD28; anti-CD3; concanavalin A; control; figure; interferon-gamma; interleukin (Il-2, IL-10 or IL-12); iron deficient; mitosis phase; monoclonal antibody against CD28 molecule; monoclonal antibody raised against CD3 (cluster of differentiation) molecule 3; newborn calf serum; pair-fed; resting phase of the cell cycle