Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
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 ISI Web of Science
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 arrow Search for citing articles in:
ISI Web of Science (6)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Turner, S. D.
Right arrow Articles by Ashby, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Turner, S. D.
Right arrow Articles by Ashby, J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Mutagenesis, Vol. 16, No. 4, 329-332, July 2001
© 2001 UK Environmental Mutagen Society/Oxford University Press

The male rat carcinogens limonene and sodium saccharin are not mutagenic to male Big BlueTM rats

Suzanne D. Turner, Helen Tinwell1,, Walter Piegorsch2,, Peter Schmezer3, and John Ashby1,4,

Molecular Immunology Programme, The Babraham Institute, Babraham Hall, Babraham, Cambridgeshire CB24AT, 1 Syngenta Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire SK10 4TJ, UK, 2 University of South Carolina, Department of Statistics, Columbia, SC 29208, USA and 3 German Cancer Research Centre, Heidelberg, Germany

Limonene and sodium saccharin are male rat specific carcinogens giving rise to renal and bladder tumours, respectively. Both compounds give negative results in genetic toxicity assays suggesting a non-genotoxic mode of action for their carcinogenicity. The {alpha}2U-globulin accumulation theory has been invoked to explain the renal carcinogenicity of limonene: the accumulation of micro masses of calcium phosphate in the bladder, coupled with a high pH environment in the male rat bladder, has been suggested to be responsible for the bladder carcinogenicity of sodium saccharin. The implication of these proposed mechanisms is that limonene and sodium saccharin will not be mutagenic to the rat kidney and bladder, respectively. This proposal has been evaluated by assessing the mutagenic potential of the two chemicals to male lacI transgenic (Big BlueTM) rats. Male BigBlueTM rats were exposed for 10 consecutive days to either limonene in diet, at a dose level in excess of that used in the original National Toxicology Program gavage carcinogenicity bioassay, or to sodium saccharin in diet at the dose known to induce bladder tumours. The multi-site rat carcinogen 4-aminobiphenyl was used as a positive control for the experiment. Limonene failed to increase the mutant frequency in the liver or kidney of the rats, and sodium saccharin failed to increase the mutant frequency in the liver or bladder of the rats. 4-Aminobiphenyl was mutagenic to all three of these tissues. These results add further support to a non-genotoxic mechanism of carcinogenic action for both limonene and sodium saccharin.

4 To whom correspondence should be addressed. Email: john.ashby{at}syngenta.com


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
 Toxicol SciHome page
A. O. Gamer, R. Jaeckh, E. Leibold, W. Kaufmann, C. Gembardt, R. Bahnemann, and B. van Ravenzwaay
Investigations on Cell Proliferation and Enzyme Induction in Male Rat Kidney and Female Mouse Liver Caused by Tetrahydrofuran
Toxicol. Sci., November 1, 2002; 70(1): 140 - 149.
[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.