MX, a by-product of water chlorination, lacks in vivo genotoxicity in gpt delta mice but inhibits gap junctional intercellular communication in rat WB cells.

Abstract

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a by-product of water chlorination, is a potent bacterial mutagen and rat carcinogen. In the present study, the in vivo mutagenicity, cell proliferative activity, and carcinogenicity of MX were investigated in gpt delta mice. Groups of 5 male and female 7-week-old gpt delta C57BL/6J transgenic mice were given MX at doses of 0, 10, 30, or 100 ppm in their drinking water for 12 weeks, and then killed to assess in vivo mutagenicity using 6-thioguanine and Spi- selection, and cell proliferative activity using immunohistochemistry for proliferating cell nuclear antigen (PCNA). Further groups of 10 male and female gpt delta mice were given 0 or 100 ppm MX for 78 weeks, and a full necropsy with histopathological examination of all organs was conducted to detect neoplastic lesions. The 12-week MX treatment did not result in mutagenicity in the livers or lungs or cell proliferative activity in several organs of the mice, and the 78-week treatment did not cause carcinogenicity. Additional investigations were conducted to evaluate the potential of MX to inhibit gap junctional intercellular communication (GJIC) in rat liver epithelial cells (WB cells) by the scrape loading/dye transfer method. Inhibition of GJIC was detected within 2 hr with a noncytotoxic dose of MX (4 microg/ml), followed by partial restoration after 5 hr. A second phase of inhibition occurred after 10 hr and then the lowered level persisted for the 24 hr-incubation period. Dose-dependent inhibition was evident at both 2 hr and 24 hr, with much stronger effects at the former time. These findings indicate that MX is not mutagenic, mitogenic or carcinogenic in mice, and suggest that the compound exerts epigenetic actions leading to GJIC inhibition.

Cite this paper

@article{Nishikawa2006MXAB, title={MX, a by-product of water chlorination, lacks in vivo genotoxicity in gpt delta mice but inhibits gap junctional intercellular communication in rat WB cells.}, author={Akiyoshi Nishikawa and Kimie Sai and Kazushi Okazaki and Hwa-Young Son and Keita Kanki and Madoka Nakajima and Naohide Kinae and Takehiko Nohmi and James Edward Trosko and Tohru Inoue and Masao Hirose}, journal={Environmental and molecular mutagenesis}, year={2006}, volume={47 1}, pages={48-55} }