Lack of modifying effects of eugenol on development of lung proliferative lesions induced by urethane in transgenic mice carrying the human prototype c-Ha-ras gene.

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  • KOUJITANI Takatoshi
    Division of Pathology, National Institute of Health Sciences
  • YASUHARA Kazuo
    Division of Pathology, National Institute of Health Sciences
  • TAMURA Toru
    Division of Pathology, National Institute of Health Sciences
  • ONODERA Hiroshi
    Division of Pathology, National Institute of Health Sciences
  • TAKAGI Hisayoshi
    Division of Pathology, National Institute of Health Sciences
  • TAKIZAWA Tamotsu
    Division of Pathology, National Institute of Health Sciences
  • HIROSE Masao
    Division of Pathology, National Institute of Health Sciences
  • HAYASHI Yuzo
    Department of Pharmaceutical Sciences, Kitasato University
  • MITSUMORI Kunitoshi
    Division of Pathology, National Institute of Health Sciences Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology

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To investigate the modifying effects of eugenol (EUG), a component of cigarette smoke, on lung carcinogenesis, male and female transgenic mice carrying the human prototype c-Ha-ras gene (rasH2 mice) were given a single intraperitoneal injection of 250 mg/kg urethane (UR) or saline, followed by a diet containing 6,000 ppm EUG or basal diet for 26 weeks. Their non-transgenic CB6F1 littermates (non-Tg mice) were also treated in the same manner. In both male and female rasH2 mice, alveolar/bronchiolar hyperplasias, adenomas and carcinomas were observed in all UR-treated groups. However, there were no significant intergroup differences in the incidences and multiplicities of these lesions between the UR alone and UR+EUG groups. In non-Tg mice, alveolar/bronchiolar hyperplasias, adenomas or carcinomas were sporadically observed in UR-treated groups of both sexes, with no significant differences in the incidences and multiplicities between the UR alone and UR+EUG groups. There were no intergroup differences between them in the PCNA-positive ratios of adenomas or carcinomas and the areas of adenomas or carcinomas to the whole lung area examined. The present results suggest that the EUG treatment does not exert modifying effects on lung carcinogenesis induced by UR in both male and female rasH2 mice and non-Tg mice.

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