Department of Environmental Oncology

Professor: Hiroshi Kasai (Ph.D.)
Research Associate: Hiroyuki Kamiya (Ph.D.)
Research Associate: Takeshi Hirano (MD, Ph.D.)


Focus of research

  1. Analysis of environmental mutagens.
  2. Mechanism of carcinogenesis induced by oxygen radicals
  3. Risk assessment of chemical carcinogens by analysis of DNA adducts

Key words
Oxygen radicals / 8-hydroxyguanine / 2-hydroxyadenine / Carcinogenesis

The primary objective of Environmental oncology is the prevention of occupational cancer. For this purpose, 1) detection and identification of environmental mutagens and carcinogens, 2) their interaction with cellular components and 3) methodology for risk assessment of newly developed chemicals are studied. Particularly mechanism of carcinogenesis induced by oxygen radicals is studied.
Oxygen radicals are produced by ionizing radiation and many other environmental carcinogens. They are also produced in cells endogenously by the oxygen metabolism. In 1984, we first reported the formation of 8-hydroxyguanine (8-OH-Gua) in DNA by oxygen radicals (Nucl. Acids Res.12,2127-2136). An easy and sensitive analytical method for detecting 8-OH-Gua with an electrochemical detector was developed allowing its detection in cellular DNA. It has been shown that 1) 8-OH-Gua is produced in DNA of target organs of rats after administration a chemical carcinogen that induces formation of oxygen radicals; 2)E.coli or mammalian cells have an enzyme(s) for repair of 8-OH-Gua in DNA; 3) 8-OH-Gua in DNA or in nucleotide pool induces mutation. The recent topics of our study are as follows. 1) Formation of 8-OH-Gua in mouse lung DNA after an intratracheal injection of diesel exhaust particles; 2) Increased formation of 8-OH-Gua in human livers with chronic hepatitis; 3) Aging and 8-OH-Gua; 4) Formation of mutagen, glyoxal, from DNA by oxygen radicals; 5) Formation of 2-hydroxyadenine in DNA and nucleotide by oxygen radicals and its mutagenic effect; 6) Increase of 8-OH-Gua repair activity by cellular oxidative stress; 7) Physical exercise and 8-OH-Gua.


Latest publications of our research

Kamiya,H., Ueda,T., Ohgi,T., Matsukage,A., Kasai,H. Misincorporation of dAMP opposite 2-hydroxyadenine, an oxidative form of adenine. Nucleic Acids Res.,23, 761-766 (1995)

Nagashima,M., Kasai,H., Yokota,J., Nagamachi,Y., Ichinose,T., Sagai,M. Formation of an oxidative DNA damage, 8-hydroxydeoxyguanosine, in mouse lung DNA after intratracheal instillation of diesel exhaust particles and effects of high dietary fat and beta-carotene on this process. Carcinogenesis, 16, 1441-1445 (1995)

Nagashima,M., Tsuda,H., Takenoshita,S., Nagamachi,Y., Hirohashi,S., Yokota,J., Kasai,H. 8-Hydroxydeoxyguanosine levels in DNA of human breast cancers are not significantly different from those of non-cancerous breast tissues by the HPLC-ECD method. Cancer Letters, 90, 157-162 (1995)

Hirano, T., Homma, Y., Kasai, H. Formation of 8-hydroxyguanine in DNA by aging and oxidative stress. In "Oxidative Stress and Aging", Bilkhauser Verlag/Basel, pp69-76(1995)

Kamiya,H., Kasai,H. Formation of 2-hydroxydeoxyadenosine triphosphate, an oxidatively damaged nucleotide, and its incorporation by DNA polymerases. J. Biol. Chem., 270, 19446-19450 (1995)

Hirano, T., Yamaguchi, Y., Hirano, H., and Kasai, H. Age-associated change of 8-hydroxyguanine repair activity in cultured human fibroblasts. Biochem. Biophys. Res. Commun., 214, 1157-1162 (1995)

Murata-Kamiya, N., Kamiya, H., Iwamoto, N., and Kasai, H. Formation of a mutagen, glyoxal, from DNA treated with oxygen free radicals. Carcinogenesis, 16, 2251-2253 (1995)

Asami, S., Hirano, T., Yamaguchi, R., Tomioka, Y., Itoh, H., and Kasai, H. Increase of a type of oxidative DNA damage, 8-hydroxyguanine, and its repair activity in human leukocytes by cigarette smoking. Cancer Res., 56, 2546-2549 (1996)


Profile of staff

Professor: Hiroshi Kasai (Ph.D.)
Research Associate: Hiroyuki Kamiya (Ph.D.)
Research Associate: Takeshi Hirano (MD, Ph.D.)


Educational activities

  1. Mutagenicity and Carcinogenicity, Ames test
  2. Chemical Carcinogenesis, Cancer Prevention
  3. Mechanism of Carcinogenesis induced by oxygen radicals.