Abstract
BackgroundCarcinogens 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.ResultsIn 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.ConclusionsThese results strongly suggest that NS is mainly caused by structural aberrations in the nucleus during interphase of the cell cycle.
Highlights
Carcinogens are known to cause swelling of the mammalian cell nucleus
Because nuclear swelling (NS) is often observed during the mammalian chromosomal aberrations (CAs) test, we examined the relationship between NS and CAs
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 (MMC, Methyl methane sulfonate (MMS), MNNG, BP, Cyclophosphamide Monohydrate (CP), and DMBA), and a strong correlation was found between NS (%) and CAs (%) at each dosage
Summary
Carcinogens are known to cause swelling of the mammalian cell nucleus. 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. Carcinogens cause swelling of the mammalian cell nucleus, a phenomenon first reported by Page [1]. As described by Westmoreland et al, because most instances of NS are independent of abnormal enhancement of DNA synthesis [5], the mechanism of NS differs from those occurring in cellular senescence and. The correlation between NS and CAs was examined using CA tests for clastogens in the Chinese hamster lung CHL/IU cell line. NS measurements were carried out using compounds known to induce structural CAs in the mouse lymphoma L5178Y cell line. L5178Y is often used in mouse lymphoma L5178Y cell Tk
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Schedule a callMore From: Genes and environment : the official journal of the Japanese Environmental Mutagen Society
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