Skip Navigation



ToxSci Advance Access published online on April 20, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfi173
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
86/1/61    most recent
kfi173v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
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 My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Hasumura, M.
Right arrow Articles by Hirose, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hasumura, M.
Right arrow Articles by Hirose, M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Toxicological Sciences © The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received February 14, 2005
Accepted April 8, 2005

Carcinogenicity

Promotion of thyroid carcinogenesis by para-aminobenzoic acid in rats initiated with N-bis(2-hydroxypropyl)nitrosamine

M. Hasumura 1, T. Imai 1*, T. Takizawa 1, M. Ueda 1, J. Onose 1, and M. Hirose 1

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

* To whom correspondence should be addressed.
T. Imai, E-mail: imai{at}nihs.go.jp


  Abstract

Sulfonamide analogues of para-aminobenzoic acid (PABA), a precursor of folate synthesis, have beneficial effects as antifolate but thyroid peroxidase-inhibition has been reported as a side effect which results in promotion of rat thyroid carcinogenesis. In the present study, effects of PABA itself on F344 rat thyroid carcinogenesis after initiation with N-bis(2-hydroxypropyl)nitrosamine (DHPN) were evaluated. In experiment 1, rats in groups 1-4 received a single subcutaneous injection of DHPN at 2800 mg/kg, and groups 5 and 6 received vehicle saline alone. From 1 week after DHPN initiation, rats in groups 2, 3, 4 and 6 were fed basal diet containing 0.25, 0.5, 1.0 and 1.0% PABA, respectively, for 40 weeks. Rats in groups 1 and 5 received basal diet alone throughout the experiment. The final incidence of thyroid follicular cell adenomas and adenocarcinomas was significantly (p<0.05 or 0.01) increased in groups 3 and 4 as compared to group 1. No thyroid tumors were found in groups 5 and 6. In experiment 2, animals in group 1 fed basal diet alone, while groups 2 and 3 were given 0.5 and 1.0% PABA in the diet, respectively, for 2 weeks. Thyroid weights in group 3, and serum thyroid stimulating hormone level and proliferative activity of follicular cells in groups 2 and 3 were significantly (p<0.05 or 0.01) elevated. In addition, the serum thyroxine level in group 3 was significantly (p<0.05) depressed. These results clearly indicate that PABA exerts promotion/progression effects on rat thyroid carcinogenesis, due to hypothyroidism followed by negative-feedback via the thyroid-pituitary axis.

Keywords: para-aminobenzoic acid; N-bis(2-hydroxypropyl)nitrosamine; thyroid; carcinogenesis; rat.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 CarcinogenesisHome page
K. Sakano, M. Takahashi, M. Mutoh, N. Niho, M. Komiya, H. Sato, T. Tanaka, T. Sugimura, and K. Wakabayashi
Enhanced thyroid carcinogenicity of N-nitrosobis(2-oxopropyl)amine in Otsuka Long-Evans Tokushima Fatty rats, a model of type II diabetes mellitus
Carcinogenesis, October 1, 2007; 28(10): 2193 - 2198.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.