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Mutagenesis Advance Access published online on August 4, 2005
Mutagenesis, doi:10.1093/mutage/gei050
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© The Author 2005. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please email: journals.permissions@oupjournals.org
Received January 5, 2005
Revised June 8, 2005
Accepted July 15, 2005

Original article

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone [MX] shows initiating and promoting activities in a two-stage BALB/c 3T3 cell transformation assay

Madoka Nakajima 1*, Sawako Shimada 2, Miho Nagai 2, Fukutaro Mizuhashi 2, Chitose Sugiyama 3, Shuichi Masuda 3, Makoto Hayashi 4, and Naohide Kinae 3

1 Genetic Toxicology Group, Biosafety Research Center, Foods, Drugs and Pesticides, 582-2, Shioshinden, Fukude-cho, Iwata-gun Shizuoka 437-1213, Japan; Laboratory of Food Hygiene, School of Food and Nutritional Sciences, COE Program in 21st Century University of Shizuoka, 52-1, Yada, Shizuoka 422-8526, Japan
2 Genetic Toxicology Group, Biosafety Research Center, Foods, Drugs and Pesticides, 582-2, Shioshinden, Fukude-cho, Iwata-gun Shizuoka 437-1213, Japan
3 Laboratory of Food Hygiene, School of Food and Nutritional Sciences, COE Program in 21st Century University of Shizuoka, 52-1, Yada, Shizuoka 422-8526, Japan
4 Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan

* To whom correspondence should be addressed.
Madoka Nakajima, E-mail: nakajima{at}anpyo.or.jp


  Abstract

A transformation assay using BALB/c 3T3 cells was conducted on 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) to assess initiation and promotion activities of MX carcinogenesis. Statistically significant positive responses were obtained compared with the corresponding solvent controls in both the initiation assay post-treated with 12-O-tetradecanoylphorbol 13-acetate (TPA) and the promotion assay pretreated with 3-methylcholanthrene (MCA). Both TPA and MX inhibited metabolic cooperation in an assay using co-culture of V79 6-thioguanine (6-TG) sensitive and insensitive cells. However, cells isolated from transformed foci in the initiation assay did not induce any nodules after inoculation to BALB/c mice, the strain of mouse from which the transformation assay cells were derived. Although the study was carried out for 2-3 weeks, this might have been too short to develop nodules under the conditions of this experiment. This in vitro cell transformation study with MX adds supportive information to studies showing MX carcinogenicity and tumour promoter activity, and adds mechanistic understanding of the action of MX.


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