title: Involvement of p53 function in different magnitude of genotoxic and cytotoxic responses in in vitro micronucleus assays.
abstract: In in vitro micronucleus (MN) assays the sensitivity to MN induction or cytotoxicity can vary depending on the kind of cells employed. This study was conducted to examine the involvement of the p53 function in the different sensitivities between Chinese hamster lung (CHL) cells and human lymphoblastoid TK6 cells in MN assays. MN induction and cytotoxicity were compared using MN-inducing chemicals reported as DNA reactive clastogens, non-DNA reactive clastogens or aneugens. The study revealed that the maximum levels of MN induction in p53-compromised CHL cells were higher than those in p53-competent TK6 cells, but MN were significantly induced in TK6 cells at lower concentrations than in CHL cells. Most of the test chemicals produced a more severe cytotoxicity in TK6 cells, suggesting TK6 cells are more sensitive for cytotoxicity than CHL cells. An additional experiment with 9 MN inducers revealed that the magnitude of MN induction and cytotoxicity were comparable between p53-competent TK6 cells and its p53-null mutant NH32 cells at the same concentrations. Furthermore, the MN frequencies induced by methylmethane sulfonate, aphidicolin and hydroxyurea in NH32 cells were identical to those in TK6 cells at different recovery times. From these results, it is suggested that the p53 abrogation does not explain the difference in sensitivity to MN induction or cytotoxicity between CHL and TK6 cells. In this regard, p53 abrogated NH32 cells can be an option for the in vitro MN assay.
authors.affiliation: Takeda Pharmaceutical Company Limited, Fujisawa, Kanagawa, Japan. Hashimoto_Kiyohiro@takeda.co.jp
authors.forename: Kiyohiro
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Yumi
authors.initials: Y
authors.lastname: Nakajima
authors.forename: Rieko
authors.initials: R
authors.lastname: Uematsu
authors.forename: Shigeo
authors.initials: S
authors.lastname: Matsumura
authors.forename: Fumio
authors.initials: F
authors.lastname: Chatani
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D015162:Micronucleus Tests / Q000379:methods*; D009153:Mutagens / Q000633:toxicity*; D012680:Sensitivity and Specificity; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D009153:Mutagens; D016159:Tumor Suppressor Protein p53