This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Imazawa, T. Articles by Hirose, M. Search for Related Content PubMed PubMed Citation Articles by Imazawa, T. Articles by Hirose, M. Social Bookmarking                         What's this?

Sequential Alteration of Apoptosis, p53 Expression, and Cell Proliferation in the Rat Pancreas Treated with 4-Hydroxyaminoquinoline 1-Oxide

Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan, imazawa{at}nihs.go.jp

Akiyoshi Nishikawa

Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan

Kazuhiro Toyoda

Present address: Japan Tobacco Co, Ltd, 2-2-1 Toranomon, Minato-ku, Tokyo 105-8422, Japan

Fumio Furukawa

Present address: Japan Tobacco Co, Ltd, 2-2-1 Toranomon, Minato-ku, Tokyo 105-8422, Japan

Masayuki Mitsui

Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan

Masao Hirose

Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan

Changes in p53 expression, apoptosis and cell proliferation after treatment with 4-hydroxyaminoquinoline 1-oxide (4HAQO) were investigated in the rat pancreas and liver, target and nontarget organs for tumorigenesis, respectively. Male rats were given a single intravenous injection of 4HAQO at a dose of 20 mg/kg body weight and control rats received vehicle alone and were euthanized after 2—72 hours. Pancreata and livers were removed for histopathological examination, immunohistochemistry for p53 protein, PCNA and Ki-67, and TUNEL labeling and electron microscopic observation for detecting apoptosis. In the pancreas, p53 expression and apoptosis were significantly increased first at 4 and 6 hours, respectively, while no change was evident in the liver. The rates peaked at 24 hours, consistent with the peak for PCNA-labeling, while Ki-67-labeling rates peaked at 72 hours. Electron microscopically, apoptotic changes in pancreatic acinar cells were observed after 2 hours. No significant apoptosis, p53 expression or cell proliferation were noted in the pancreatic tissues of the control rats nor in liver cells regardless of 4HAQO treatment. Taken together with our previous data, the results suggest that apoptosis, p53 expression, and enhanced cell replication are closely related phenomena involved in the carcinogenesis of 4HAQO following DNA adduct formation.

Key Words: p53 protein • apoptosis • cell proliferation • 4-hydroxyaminoquinoline 1-oxide • rat • pancreas.

References

• Anderson CW (1993). DNA damage and DNA-activated protein kinase. TIBS 18: 433—437.[Medline] [Order article via Infotrieve]
• Baas IO, Muldér JR, Offerhaus JA, Vogelstein B., Hamilton SR (1994). An evaluation of six antibodies for immunohistochemistry of mutant p53 gene product in archival colorectal neoplasms. J Pathol 172: 5—12.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Coats P., Save V., Ansari B., Hall PA ( 1995). Demonstration of DNA damage/repair in individual cells using in situ end labelling: association of p53 with site of DNA damage. J Pathol 176: 19—26.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Donehower LA, Bradley A. (1993). The tumor suppressor p53. Biochem Biophys Acta 1155: 181—205.[Medline] [Order article via Infotrieve]
• Doolittle DJ, McKarns SC, Ayres PH, Bombick DW (1992). Molecular approaches for quantifying DNA synthesis and cell proliferation during rodent bioassays. Toxicol Meth 1: 215—230.
• Galiègue-Zouitina S., Bailleul B., Loucheux-Lefebvre MH (1985). Adducts from in vivo action of the carcinogen 4-hydroxyaminoquinoline 1-oxide in rats and from in vitro reaction of 4-acetoxyaminoquinoline 1-oxide with DNA and polynucleotides. Cancer Res 45: 520—525.[Abstract/Free Full Text]
• Gavrieli Y., Sherman Y., Ben-Sasson SA (1992). Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 119: 493—501.[Abstract/Free Full Text]
• Gerdes J., Lemke H., Baisch H., Wacker HH, Schwab U., Stein H. (1984). Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 133: 1710—1715.[Abstract]
• Greenblatt MS, Bennet WP, Hollstein M., Harris CC (1994). Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res 54: 4855—4878.[Free Full Text]
• Hainaut P., Milner J. (1993). Redox of p53 conformation and sequencespecific DNA binding in vitro. Cancer Res 53: 4469—4473.[Abstract/Free Full Text]
• Hall PA, McKee PH, Merage HD, Dover R., Lane DP ( 1993). High levels of p53 protein in UV-irradiated normal human skin. Oncogene 8: 203—207.[Web of Science][Medline] [Order article via Infotrieve]
• Hall PA, Lane DP ( 1994). p53 in tumor pathology: can we trust immunohistochemistry revisited. J Pathol 172: 1—4.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Harris CC (1993). p53: at the crossroads of molecular carcinogenesis and risk assessment. Science 262: 1980—1981.[Free Full Text]
• Hayashi Y., Hasegawa T. (1970). Nucleolar alterations of alveolar epithelial cells in rats following a single injection of 4-nitroquinoline 1-oxide. Gann 61: 347—352.[Web of Science][Medline] [Order article via Infotrieve]
• Hayashi, Y. Hasegawa T. (1971). Experimental pancreatic tumors in rats after intravenous injection of 4-hydroxyaminoquinoline 1-oxide. Gann 62: 329—330.[Web of Science][Medline] [Order article via Infotrieve]
• Hayashi Y., Furukawa H., Hasegawa T. (1972). Pancreatic tumors in rats induced by 4-nitroquinoline 1-oxide derivatives. In: Topics in Chemical Carcinogenesis, Nakahara W, Takayama S, Sugimura T, Odashima S (eds). University Park Press, Baltimore, pp 53—72.
• Imazawa T., Nishikawa A., Shibutani M., Ogasawara H., Furukawa F., Ikeda T., Suda K., Hirose M. (2001). Induction of pancreatic islet cell tumors in rats by repeated intravenous administration of 4-hydroxyaminoquinoline 1-oxide. Toxicol Pathol 29: 320—327.[Abstract/Free Full Text]
• Imazawa T., Nishikawa A., Tada M., Takahashi M., Hayashi Y. (1995). Nucleolar segregation as an early marker for DNA damage; an experimental study in rats treated with 4-hydroxyaminoquinoline 1-oxide. Virchows Arch 426: 295—300.[Web of Science][Medline] [Order article via Infotrieve]
• Kastan MB, Onyerkwere O., Sidransky D., Vogelstein B., Craig RW (1991). Participation of p53 protein in the cellular response to DNA damage. Cancer Res 51: 6304—6311.[Abstract/Free Full Text]
• Kelman Z. (1997). PCNA: structure, functions and interactions. Oncogene 14: 629—640.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Kemp CJ (1995). Hepatocarcinogenesis in p53-defiecient mice. Mol Carcinogen 12: 132—136.[Web of Science][Medline] [Order article via Infotrieve]
• Kisilevsky R. (1974). Hepatic nuclear and nucleolar changes in amanita poisoning. Arch Pathol 97: 253—258.[Web of Science][Medline] [Order article via Infotrieve]
• Konishi Y., Maruyama H., Mii Y., Miyauchi Y., Yokose Y Masuhara K. (1982). Malignant fibrous histocytomas induced by 4-hydroxyaminoquinoline 1-oxide in rats. J Natl Cancer Inst 68: 859—865.[Web of Science][Medline] [Order article via Infotrieve]
• Lane DP, Benchimol S. (1990). p53: oncogene or anti-oncogene. Genes Dev 4: 1—8.[Free Full Text]
• Lowe SW, Schmitt EM, Smith SW, Osborne BA, Jacks T. (1993). p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature 362: 847—849.[CrossRef][Medline] [Order article via Infotrieve]
• Miller EC (1978). Some current perspectives on chemical carcinogensis in humans and experimental animals: Presidential address. Cancer Res 38: 1479—1496.[Free Full Text]
• Milne DM, Campbell DG, Caudwell FB, Meek W. ( 1994). Phosphorylation of the tumor supressor protein p53 by mitogen-activated protein kinases. J Biol Chem 269: 9253—9260.[Abstract/Free Full Text]
• Mori K., Ohta A., Murakami T., Tamura M., Kondo M., Ichimura H. (1969). Carcinomas of the glandular stomach and other organs of rats by 4-hydroxyaminoquinoline 1-oxide hydrochloride. Gann 60: 627—630.[Web of Science][Medline] [Order article via Infotrieve]
• Mosner J., Deppert W (1994). p53 and mdm2 are expressed independently during cellular proliferation. Oncogene 9: 3321—3328.[Web of Science][Medline] [Order article via Infotrieve]
• Nakagawa K., Tada M., Morita T., Utsunomiya J., Ishikawa T. (1988). Immunohistochemical detection of 4-hydroxyaminoquinoline 1-oxide-DNA adducts in mouse tissues in vivo. J Natl Cancer Inst 80: 419—425.[Abstract/Free Full Text]
• Poirier MC (1981). Antibodies to carcinogen-DNA adducts. J Natl Cancer Inst 67: 515—519.[Web of Science][Medline] [Order article via Infotrieve]
• Raff MC (1992). Social controls on cell survival and cell death. Nature 356: 398—400.
• Rao MS, Upton MP, Subbarao V., Scarpelli DG (1982). Two populations of cells with differing proliferative capacities in atypical acinar cell foci induced by 4-hydroxyaminoquinoline 1-oxide in the rat pancreas. Lab Invest 46: 527—534.[Web of Science][Medline] [Order article via Infotrieve]
• Shi SR, Key ME, Kalra KL (1991). Antigen retrieval in formalin-fixed, paraffin-embedded tissues: an enhancement method forimmunohistochemical staining based on microwave oven heating of tissue sections. J Histochem Cytochem 39: 741—748.[Abstract]
• Shivakumar CV, Brown DR, Deb S., Deb SP (1995). Wild-type human p53 transactivates the human proliferating cell nuclear antigen promoter. Mol Cell Biol 15: 6785—6793.[Abstract]
• Sugimura T. (1981). The nitroquinolines. In: Carcinogenesis, Sugimura T (ed). Raven Press, New York, Vol 6, pp 1—153.
• Tada M., Kohda KH, Kawazoe Y. (1984). Biomimetic preparation and structure determination of QGI, one of the quinoline-DNA base adducts formed in cells treated with 4-nitroquinoline 1-oxide. Gann 75: 976— 985.[Web of Science][Medline] [Order article via Infotrieve]
• Toschi L., Bravo R. (1988). Changes in cyclin/proliferating cell nuclear antigen distribution during DNA repair synthesis. J Cell Biol 107: 1623—1628.[Abstract/Free Full Text]
• van Dierendonck JH, Wijsman JH, Keijzer R., van de Velde Cjh, Cornelisse CJ (1991). Cell-cycle-related staining patterns of anti-proliferating cell nuclear antigen monoclonal antibodies. Am J Pathol 138: 1165— 1172.[Abstract]
• Williams GT (1991). Programmed cell death: apoptosis and oncogenesis. Cell 65: 1097—1098.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Yonishi-Rouach E. (1991). Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6. Nature 352: 345—347.[CrossRef][Medline] [Order article via Infotrieve]

Toxicologic Pathology, Vol. 31, No. 6, 625-631 (2003)
DOI: 10.1080/01926230390241855


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Imazawa, T. Articles by Hirose, M. Search for Related Content PubMed PubMed Citation Articles by Imazawa, T. Articles by Hirose, M. Social Bookmarking                         What's this?