title: Structural chromosome aberrations cause swelling of the nucleus.
abstract: BACKGROUND
  Carcinogens are known to cause swelling of the mammalian cell nucleus. However, the mechanism of the swelling and its toxicological significance have not been fully elucidated. Since nuclear swelling (NS hereafter) has been frequently observed in chromosomal aberration (CA hereafter) tests (in vitro), the relationship between NS and CAs was investigated in this study.
  
  
  RESULTS
  In a short-term CA test using the fibroblast CHL cell line, the appearance of NS increased in a dose-dependent manner after exposure to six types of clastogens (mitomycin C, methyl methane sulfonate, 1-methyl-3-nitro-1-nitrosoguanidine, benzo[a]pyrene, cyclophosphamide monohydrate, and 9,10-dimethyl-2-benzanthracene), and a strong correlation was found between NS (%) and CAs (%) at each dosage. Therefore, we hypothesized that clastogens cause NS in cultured mammalian cells, since the mouse lymphoma L5178Y cell line is known to have a similar sensitivity to clastogens. Thus, we measured NS for 14 compounds (clastogens) that are known to induce structural CAs, 4 aneugens, and 12 non-mutagenes. Almost all clastogens caused NS of more than 5 %, which increased in a dose-dependent manner. Among the aneugens, colchicine, and diethylstilbestrol caused the same level of NS % as the clastogens, while carbendazim and trichlorfon caused a similar level of NS % as the clastogens only at higher levels of cytotoxicity. Almost all the non-mutagens caused less than 5 % NS.
  
  
  CONCLUSIONS
  These results strongly suggest that NS is mainly caused by structural aberrations in the nucleus during interphase of the cell cycle.
authors.affiliation: Department of Biological Functions Engineering, Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, 2-4 Hibikino, Wakamatsu-ku, Fukuoka, 808-0196 Japan ; UBE Scientific Analysis Laboratory, Inc, 1978-5 Kogushi, Ube, Yamaguchi 755-8633 Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Takeshita
authors.affiliation: Department of Biological Functions Engineering, Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, 2-4 Hibikino, Wakamatsu-ku, Fukuoka, 808-0196 Japan.
authors.forename: Hiroaki I
authors.initials: HI
authors.lastname: Ogawa
authors.affiliation: Department of Biological Functions Engineering, Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, 2-4 Hibikino, Wakamatsu-ku, Fukuoka, 808-0196 Japan.
authors.forename: Toshinari
authors.initials: T
authors.lastname: Maeda
keywords: Aneugen; Carcinogen; Chromosomal aberration; Clastogen; Genotoxicity; Non-mutagen; Nuclear swelling