Cadmium and T cell differentiation: Limited impact in vivo but significant toxicity in fetal thymus organ culture

• Published in: Toxicology and applied pharmacology 2007-09, Vol.223 (3), p.257-266
• Main Authors: Viau, Muriel, Collin-Faure, V., Richaud, P., Ravanat, J.-L., Candéias, S.M.
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Apoptosis - radiation effects; Biological and medical sciences; CADMIUM; Cadmium Chloride - pharmacokinetics; Cadmium Chloride - toxicity; Carcinogens, Environmental - pharmacokinetics; Carcinogens, Environmental - toxicity; CELL CYCLE; CELL DIFFERENTIATION; Cell Differentiation - drug effects; Cells, Cultured; Chemical and industrial products toxicology. Toxic occupational diseases; DNA; DNA Damage; DRINKING WATER; EXCISION REPAIR; Female; FTOC; GAMMA RADIATION; Gamma Rays; GLUTATHIONE; Immunology; Immunotoxicity; IN VIVO; Life Sciences; LYMPHOCYTES; Medical sciences; Metals and various inorganic compounds; MICE; Mice, Inbred C57BL; NUCLEOTIDES; Organ Culture Techniques; Oxidative DNA lesions; OXYGEN; Pregnancy; RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS; RECEPTORS; RECOMBINATION; Spleen - drug effects; Spleen - pathology; STRAND BREAKS; T-Lymphocytes - drug effects; T-Lymphocytes - pathology; Thymocyte differentiation; THYMOCYTES; THYMUS; Thymus Gland - drug effects; Thymus Gland - embryology; Thymus Gland - pathology; Thymus Gland - radiation effects; TISSUE CULTURES; Tissue Distribution; TOXICITY; Toxicology
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2007.05.017

DNA lesions, including oxydated bases, nucleotide damage and double strand breaks, are continuously produced in living cells and represent a threat for genetic stability. Highly conserved repair processes have evolved to maintain DNA integrity. Cadmium (Cd) is an environmental carcinogenic pollutant known to inactivate several proteins involved in DNA repair systems while at the same time creating an oxidative stress that can result in additional DNA lesions. Cd also has potent immunotoxic effects. DNA repair by non-homologous end joining (NHEJ) is absolutely required for T lymphocyte differentiation. In this study, we examined the impact of Cd on non-homologous end joining pathway by analyzing T cell development in the thymus of mice that received Cd-supplemented drinking water. In vivo, the absence of major alteration indicates that Cd does not affect NHEJ, despite its accumulation in the thymus. Cd contamination affects only a discrete population of developing thymocytes. However, these cells are functional as the cellular response observed in mice following γ-radiation exposure is identical in treated and control mice. Furthermore, Cd diet did not perturb the redox status in thymocytes and more importantly did not generate significant DNA lesions in organs that accumulate the highest concentration of Cd. Our results show that in vivo, Cd does not affect NHEJ or base and nucleotide repair, and that Cd toxicity to T cells is rather linked to cell cycle perturbations.