4-chloro-1,2-phenylenediamine Induces Apoptosis in Mardin–Darby canine kidney cells via activation of caspases

Authors

  • Leong Chee Onn,

    1. Department of Life Science, School of Pharmacy and Health Science, International Medical University, No. 126, Jalan 19/155B, Bukit Jalil, 57000 Kuala Lumpur, Malaysia
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  • Chen Ssu Ching,

    1. Department of Biotechnology, National Kaohsiung Normal University, 116 Ho-Ping First Road, Lin-Ya 802, Kaohsiung, Taiwan
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  • Tiong Yee Lian,

    1. Department of Biosciences and Chemistry, Faculty of Engineering and Science, Universiti Tunku Abdul Rahman, Jalan Genting Klang, Setapak, 53300 Kuala Lumpur, Malaysia
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  • Loh Veng Foon,

    1. Division of Pharmacy, School of Pharmacy and Health Science, International Medical University, No. 126, Jalan 19/155B, Bukit Jalil, 57000 Kuala Lumpur, Malaysia
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  • Ng Chew Hee,

    1. Department of Biosciences and Chemistry, Faculty of Engineering and Science, Universiti Tunku Abdul Rahman, Jalan Genting Klang, Setapak, 53300 Kuala Lumpur, Malaysia
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  • Chye Soi Moi

    Corresponding author
    1. Department of Human Biology, School of Medicine, International Medical University, No. 126, Jalan 19/155B, Bukit Jalil, 57000 Kuala Lumpur, Malaysia
    • Department of Human Biology, School of Medicine, International Medical University, No. 126, Jalan 19/155B, Bukit Jalil, 57000 Kuala Lumpur, Malaysia. E-mail: chye_soimoi@imu.edu.my

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Abstract

4-Chloro-1,2-phenylenediamine (4-Cl-o-PD) is a halogenated aromatic diamine that was used as a precursor for manufacturing permanent hair dyes. Despite its well-documented mutagenic and carcinogenic effects in a number of in vitro and in vivo models, its cytotoxicity and mode of action have not received similar attention. Here, we investigated the effect of 4-Cl-o-PD on Mardin–Darby canine kidney cells. It induced apoptosis and the evidence suggests its initiation by reactive oxygen species (ROS). The results of various assays used show a dose-dependent (i) decrease in cell viability, (ii) increase in cells at sub-G1 phase and the G0/G1 phase arrested in cell cycle, (iii) increase in intracellular ROS accompanied by depletion of glutathione, and (iv) that apoptotic cell death probably involves activation of both intrinsic and extrinsic pathways. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 655–664, 2014.

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