Toxicologic Pathology

 

Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Click here to sign up for SAGE Journal Email Alerts today!

Sign In to gain access to subscriptions and/or personal tools.
This Article
Right arrow Free Full Text (Free PDF) Free
Right arrow References
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Imazawa, T.
Right arrow Articles by Hirose, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Imazawa, T.
Right arrow Articles by Hirose, M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
Toxicologic Pathology, Vol. 31, No. 6, 625-631 (2003)
DOI: 10.1080/01926230390241855

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

Takayoshi Imazawa

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.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?