Risk Assessment of Carcinogenesis due to Environmental Agents

2000 Fiscal Year Final Research Report Summary

• Project/Area Number: 09253105
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Research Institution: Osaka City University Medical School
• Principal Investigator: FUKUSHIMA Shoji First Department of Pathology, Osaka City University Medical School, Professor, 医学部・第一病理学教室, 教授 (00137077)
• Co-Investigator(Kenkyū-buntansha): TSUDA Hiroyuki Chemotherapy Division, National Cancer Center Research Institute, Chief, 化学療法部, 部長 (10163809) ; TATEMATSU Masae Laboratory of Pathology, Aichi Cancer Center Research Institute, Chief, 病理, 部長 (70117836) ; HIROSE Masao Division of Pathology, National Institute of Health Sciences, Chief, 病理部, 部長 (90145748) ; IMAIDA Katsumi First Department of Pathology, Nagoya City University Medical School, Assistant Professor, 医学部・病理学, 助教授 (90160043) ; NAKAE Dai Department of Oncological Pathology, Nara Medical University, Assistant Professor, 腫瘍病理, 助教授 (90207712)
• Project Period (FY): 1996 – 1999
• Keywords: cancer risk assessment / environmental carcinogen / heterocyclic amine / diethylnitrosamine / preneoplastic lesions / mutation frequency / in vivo mutagenicity / 8-hydoxyguanine

Research Abstract

1) It was strongly suggested that a no observed effect level exists for rat liver carcinogenicity of diethylnitrosamine. 2) SCID mice proved useful for detection of 2-amino-3-methylimidazo [4,5-f] quinoline-low dose carcinogenicity. 3) Phenobarbital treatment to rats induced P450 and hydroxyradicals in the liver, resulting in increase of 8-hydroxyguanine (8-OHG) formation. 4) Further studies are required risk assessment for carcinogenesis using transgenic or knockout mice. 5) PLACE-SSCP method was examined to confirm the utility of detection for rare mutations of oncogenes or tumor suppressor genes related to cancer induction. 6) Mesurement of 8-OHG is important for risk assessment of carcinogenesis in animals.

Research Products

• [Publications] Salim,E.I., Fukushima,S. et al.: "Low dose-dependent carcinogenic potential of 2-amino-3-methylimidazo[4,5-f]quinoline in the immunodeficient (SCID) mouse colon."Nutrition and Cancer. 34. 220-228 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Nishikawa,A., Hirose,M. et al.: "Trans-4-hydroxy-2-nonenal, an aldehydic lipid peroxidation products, lacks genotoxicity in lacl transgenic mice."Cancer Lett.. 148. 81-86 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tsukamoto,T.,Tatematsu,M. et al.: "Development and distribution of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced aberrant crypt foci in the rat large intestine. "Jpn.J.Cancer Res.. 90. 720-725 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tsuda,H. et al.: "Heterocyclic amine mixture carcinogenesis and its enhancement by caffeine in F344 rate."Cancer Lett.. 143. 229-234 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Yoshida,M., Nakae,D., et al.: "Hepatocoxicity and consequently increased cell proliferation are associated with flumequine hepatocarcinogenesis in mice."Cancer Lett.. 141. 99-107 (2000)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Imaida, K. et al.: "Delay of DNA- adduct repair and severe toxicity in xeroderma pigmentosum group A gene (XPA) deficient mice treated with 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)."Cancer Lett.. 144. 1-7 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Fukushima, S. et. al.: "Differences of promoting activity and loss of heterozygosity between dimethylarsinic acid and sodium L-ascorbate in F1 rat urinary bladder carcinogenesis. In : Arsenic exposure and health effects."Elsevier, Tokyo (eds.) Chappell,W.R., Abemathy,C.O., Calderon,R.L.. 4 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Salim, E.I., Fukushima, S., et al.: "Low-dose-dependent carcinogenic potential of 2-amino-3-methylimidazo [4,5-f] quinoline in the immunodeficient (SCID) mouse colon."Nutrition and Cancer. 34. 220-228 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Nishikawa, A., Hirose, M.: "Trans-4-hydroxy-2-nonenal, an aldehydic lipid peroxidation products, lacks genotoxicity in lacI transgenic mice."Cancer Lett.. 148. 81-86 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tsukamoto, T., Tatematsu, M.: "Development and distribution of 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP)-induced aberrant crypt foci in the rat large intestine."Jpn.J.Cancer Res.. 90. 720-725 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tsuda, H., et al.: "Heterocyclic amine mixture carcinogenesis and its enhancement by caffeine in F344 rats."Cancer Lett.. 143. 229-234 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Yoshida, M., Nakae, D.et al.: "Hepatocoxicity and consequently increased cell proliferation are associated with flumequine hepatocarcinogenesis in mice."Cancer Lett.. 141. 99-107 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Imaida, K., et al.: "Delay of DNA-adduct repair and severe toxicity in xeroderma pigmentosum group A gene (XPA) deficient mice treated with 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP)."Cancer Lett.. 144. 1-7 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Chen, T., Fukushima, S.et al.: "Differences of promoting activity and loss of heterozygosity between dimethylarsinic acid and sodium L-ascorbate in F1 rat urinary bladder carcinogenesis. In : Arsenic exposure and health effects."(eds.) Chappell, W.R., Abernathy, C.O., Calderon, R.L., Elsevier, Tokyo. 263-266 (1999)
  • Description: 「研究成果報告書概要(欧文)」より