DNA oxidative damage caused by the aromatic amine MOCA —Examination of 8-hydroxy-2’-deoxyguanosine levels in rat liver—

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  • KOBAYASHI Saho
    Division of Industrial Toxicology, Research Center for Chemical Information and Management, National Institute of Occupational Safety and Health, Japan
  • MOTOOKA Yashiro
    Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya, Japan Japan
  • KASHIWAGI Hiroki
    Division of Industrial Toxicology, Research Center for Chemical Information and Management, National Institute of Occupational Safety and Health, Japan
  • TOYOKUNI Shinya
    Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya, Japan Japan

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  • 芳香族アミン類MOCAのDNA酸化損傷に関する研究 －ラット肝臓における8 -ヒドロキシ-2’-デオキシグアノシンの検討－
  • ホウコウゾク アミンルイ MOCA ノ DNA サンカ ソンショウ ニ カンスル ケンキュウ : ラット カンゾウ ニ オケル 8-ヒドロキシ-2'-デオキシグアノシン ノ ケントウ

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Abstract

<p>MOCA (4,4’-methylenebis (2-chloroaniline)) , an aromatic amine, is industrially used as a curing agent for urethane resins; however, it is classified as a Group 1 compound (carcinogenic to humans) by the International Agency for Research on Cancer, and there is concern regarding its health effects on workers. The mechanism underlying MOCA-mediated carcinogenesis is thought to be related to DNA damage caused by reactive oxygen species (ROS) and DNA adducts, which are mainly generated during metabolism in the liver. 8-Oxoguanine (8-OHdG), a product of ROS-induced oxidation, occurs at high frequency and can induce G→T transversion mutations during DNA replication. However, to the best of our knowledge, no study has examined whether MOCA induces the formation of highly mutagenic 8-OHdG in experimental animals. Here, F344 rats were orally exposed to 0, 0.4, 2, 10, or 50 mg/kg/day MOCA three times a week for 2 weeks; this is expected to exert toxicity through the hepatic metabolism of MOCA. Livers obtained from these animals were examined for pathology and 8-OHdG levels. In pathological sections, vacuolar degeneration was observed with 50 mg/kg/day MOCA. Further, MOCA-induced 8-OHdG levels showed a slight increasing trend, except at 0.4 mg/kg/day. However, none of these differences were significant. Thus, 8-OHdG is unlikely the main cause of carcinogenesis.</p>

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