Suppression of Hela cell growth and increase in nuclear size by chemical carcinogens: A possible screening method

Grant, Debra; Grasso, P.

doi:10.1016/0027-5107(78)90221-x

Cited by 13 publications

(3 citation statements)

References 28 publications

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“…The nuclear enlargement was reported to occur as an early histopathological change induced by chemical carcinogens in the upper respiratory tract of rats exposed to sulphur dioxide and intraperitoneally injected with several N-nitrosamines which are known to induce nasal tumors in rats (Fowlie et al, 1990). Grant and Grasso (1978) reported that there is a good correlation between in vivo carcinogenicity and the extent of nuclear enlargement in HeLa cells in vitro. Therefore, the nuclear enlargement found in the present study might be causally related to the possible development of carcinogenicity by 1,4-dioxane in the upper respiratory tract of rats and mice.…”

Section: Discussionmentioning

confidence: 99%

Thirteen-week oral toxicity of 1,4-dioxane in rats and mice

et al. 2008

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Subchronic oral toxicity of 1,4-dioxane was examined by administering 1,4-dioxane in drinking water at 6 different concentrations of 0 (control), 640, 1,600, 4,000, 10,000 or 25,000 ppm (wt/wt) to F344 rats and BDF(1)mice of both sexes for 13 weeks. Food and water consumption and terminal body weight were decreased dose-dependently in rats and mice. A dose-dependent increase in the relative weights of kidney and lung was noted in rats and mice, while the relative liver weight was increased only in rats. Increases in plasma levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and a decrease in plasma glucose were noted primarily in the rats and mice dosed 25,000 ppm. Histopathological examination revealed that 1,4-dioxane affected the upper and lower respiratory tracts, liver, kidneys and brain in rats, while only the former two organs were affected in mice. Nuclear enlargement occurred in the respiratory, olfactory, tracheal and bronchial epithelia of the 1,4-dioxane-dosed rats and mice. The 1,4-dioxane-induced hepatic lesions were characterized by centrilobular swelling and necrosis in rats and mice and by glutathione S-transferase placental form (GST-P)-positive altered hepatocellular foci in rats, which are known as preneoplastic lesions. A no-observed-adverse-effect-level (NOAEL) was determined at 640 ppm for both rats and mice, since the nuclear enlargement in the nasal respiratory epithelium and the centrilobular swelling of hepatocytes in rats and the nuclear enlargement in the bronchial epithelium in mice were observed at 1,600 ppm. The NOAEL value corresponded to the estimated 1,4-dioxane intake of 52 mg/kg/day in rats and 170 mg/kg/day in mice.

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Section: Discussionmentioning

confidence: 99%

Thirteen-week oral toxicity of 1,4-dioxane in rats and mice

et al. 2008

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“…Numerous studies have evaluated nuclear swelling (NS), including in cultured mammalian cells (e.g., HeLa S3 cells) by Agrelo [ 2 ]. Grant and Finch et al proposed a screening test (nuclear enlargement assay) for identifying carcinogens based on NS [ 3 , 4 ]. However, 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 cancerous cells [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Structural chromosome aberrations cause swelling of the nucleus

2016

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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.

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“…*" Increased nuclear size has been observed also in a variety of cultured cell^.^'-^^. Grant and Grasso (1978)'s undertook a systematic investigation using a variety of compounds and found a good correlation between in vivo carcinogenicity and the extent of nuclear enlargement in HeLa cells in vitro. This was confirmed by further work of Agrelo (1978)2h and Agrelo and Amos (1981).…”

Section: Introductionmentioning

confidence: 99%

The short‐term effects of carcinogens and sulphur dioxide on the nuclear size of rat nasal epithelial cells

Fowlie

Grasso

Benford

1990

J of Applied Toxicology

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Enlarged nuclei have been observed frequently as an early carcinogen-induced change in both cultured cells and in target tissues in vivo. The purpose of this work was to examine the occurrence of nuclear enlargement in the upper respiratory tract of rats to provide further evidence of whether nuclear enlargement is a reliable marker of carcinogenesis, and if it could be used as a short-term test for respiratory carcinogens. Carcinogen-induced nuclear enlargement is best demonstrated in vivo when the tissue involved has been undergoing rapid replication. Male Wistar albino rats were simultaneously exposed to an atmosphere containing sulphur dioxide (which caused a hyperplastic response in the nasal cavity) and received an i.p. injection of a nitrosamine. Sections were prepared from the nasal cavity, and the nuclear areas of respiratory epithelial cells were measured. There were some increases in nuclear size 24 and 72 h after the start of treatment. The reversal of this effect 120 h after the start of treatment may have been due to the loss of the normal ciliated mucosal epithelium, and subsequent loss of metabolic capability.

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Suppression of Hela cell growth and increase in nuclear size by chemical carcinogens: A possible screening method

Cited by 13 publications

References 28 publications

Thirteen-week oral toxicity of 1,4-dioxane in rats and mice

Thirteen-week oral toxicity of 1,4-dioxane in rats and mice

Structural chromosome aberrations cause swelling of the nucleus

The short‐term effects of carcinogens and sulphur dioxide on the nuclear size of rat nasal epithelial cells

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