Changes in fluoride sensitivity during in vitro senescence of normal human oral cells.
We have previously reported that sodium fluoride (NaF) showed slightly higher cytotoxicity against human oral tumor cell lines than normal human oral cells. Possible changes in the NaF sensitivity of three normal human oral cell types (gingival fibroblast HGF, pulp cell HPC, periodontal ligament fibroblast HPLF) during in vitro ageing were investigated in the present study. When these cells were subcultured at 1:4 split ratio every week, their saturation density declined with increasing population doubling level (PDL), and they ceased to divide when they reached 20 PDL. Mitochondrial function, evaluated by MTT stainability per cell basis, was elevated at the terminal phase. NaF dose-dependently reduced the viable cell number, but did not show any beneficial (growth promoting) effect (so-called "hormesis") at lower concentrations. NaF produced large DNA fragments, without induction of internucleosomal DNA fragmentation, possibly due to weak activation of caspases -3, -8 and -9. Higher concentrations of NaF were required to reduce the number of viable senescent cells than younger cells, indicating that cells become resistant to cytotoxicity of NaF with in vitro ageing.
Satoh
Rie
R
Department of Dental Pharmacology, Meikai University School of Dentistry, Sakado, Saitama 350-0283, Japan.
Kishino
Kaori
K
Morshed
Sufi Reza Md
SR
Takayama
Fumitoshi
F
Otsuki
Sumiko
S
Suzuki
Fumika
F
Hashimoto
Ken
K
Kikuchi
Hirotaka
H
Nishikawa
Hirofumi
H
Yasui
Toshikazu
T
Sakagami
Hiroshi
H
D048708:Cell Growth Processes / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects; D002648:Child; D053938:DNA Fragmentation / Q000187:drug effects; D003786:Dental Pulp Cavity / Q000166:cytology / Q000187:drug effects; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005881:Gingiva / Q000166:cytology / Q000187:drug effects; D006801:Humans; D009055:Mouth / Q000166:cytology* / Q000187:drug effects*; D009707:Nucleosomes / Q000187:drug effects; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects; D012969:Sodium Fluoride / Q000494:pharmacology*
D009707:Nucleosomes; D012969:Sodium Fluoride