title: Cadmium-induced adaptive response in cells of Chinese hamster ovary cell lines with varying DNA repair capacity.
abstract: The combined exposure to environmental toxicants such as heavy metals and radiation is an important research area in health protection. The aim of this study was to investigate the role of DNA repair and the phosphatidylinositol 3-kinase (PI3K) family in the cadmium-induced adaptive response to toxicants or radiation. Using cells of three Chinese hamster ovary (CHO) cell lines with different capacities to repair DNA damage, we found that pre-exposure to cadmium at a nonlethal concentration could induce an adaptive response to a subsequent challenge with cadmium or radiation in all the cell lines. The magnitude of the adaptive response in adapted cells was dependent on several factors, including DNA repair capacity, the priming dose of cadmium, and the challenging dose of cadmium or radiation. When the cells were challenged with 50 microM CdCl2, the adaptive response was less evident in XRCC1-defective EM-C11 cells than in cells of the other two cell lines. Moreover, treatment of cells with wortmannin or KU-55933 eliminated the adaptive response in all the cell lines. Our data suggest that the triggering of a cadmium-induced adaptive response was independent of DNA repair capacity. Single-strand break (SSB) repair or base excision repair (BER) rather than double-strand break (DSB) repair was mainly involved in the adaptive response. This response of cells to a further challenge with cadmium or radiation may be mediated through the ataxia telangiectasia mutated (ATM) pathway.
authors.affiliation: Institute of Radiation Medicine, Fudan University, Shanghai 200032, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Pan
authors.forename: Dexiao
authors.initials: D
authors.lastname: Yuan
authors.forename: Junxiang
authors.initials: J
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
authors.forename: Honghong
authors.initials: H
authors.lastname: Chen
authors.forename: Chunlin
authors.initials: C
authors.lastname: Shao
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D016466:CHO Cells; D002104:Cadmium / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015162:Micronucleus Tests; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011753:Pyrones / Q000494:pharmacology; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D064007:Ataxia Telangiectasia Mutated Proteins; D002104:Cadmium; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011753:Pyrones; D025521:Tumor Suppressor Proteins; D000077191:Wortmannin; C495818:2-morpholin-4-yl-6-thianthren-1-yl-pyran-4-one