Document Detail


Experimental investigations into the carcinogenic effect of antitumor and immunosuppressive agents.
MedLine Citation:
PMID:  2760096     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In a comprehensive experimental study on rats, the carcinogenicity of various therapeutically important antitumor drugs was investigated. The influences of strain, sex, dose and time of administration were systematically varied. The tested compounds showed remarkable differences in their carcinogenic potential. These differences were particularly obvious, not only when the total tumor rate was analyzed, but also when the distribution of tumor rates to the various localizations was considered (tumor spectrum). Three classes of carcinogenic substances were identified: (1) Substances showing a specific carcinogenicity: they lead to tumorogenesis primarily in organs or organ systems that, in the untreated control animals, remain virtually tumor-free for life. One example of such a substance is chlormethine. (2) Substances with non-specific carcinogenicity: they lead to an increase in tumors in organs that are also stricken in the control animals, however, to a clearly reduced extent. Oxazaphosphorine carcinogenicity is typical for this class. (3) Substances of mixed-type carcinogenicity: this group shows non-specific carcinogenicity, as well as a carcinogenic action with marked organ specificity. One example of this class is procarbazine. The antimetabolites tested were shown to be practically non-carcinogenic. Characteristic differences occurred between the two rat strains used in the investigation, Sprague-Dawley and BD II, with regard to the spontaneous tumor spectrum and the organ-related extent of carcinogenicity under the influence of the substances tested. In an experiment involving short-term application (up to 17% LD50, five times i.v. at 14-day intervals), the carcinogenic effects were substantially lower than in an experiment involving long-term application (up to 7% LD50, once a week for 52 weeks, i.v.), although the strain- and substance-specific characteristics in both experiments were rather similar.
Authors:
N Brock; B Schneider; J Stekar; J Pohl
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cancer research and clinical oncology     Volume:  115     ISSN:  0171-5216     ISO Abbreviation:  J. Cancer Res. Clin. Oncol.     Publication Date:  1989  
Date Detail:
Created Date:  1989-09-19     Completed Date:  1989-09-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7902060     Medline TA:  J Cancer Res Clin Oncol     Country:  GERMANY, WEST    
Other Details:
Languages:  eng     Pagination:  309-28     Citation Subset:  IM    
Affiliation:
Department of Experimental Cancer Research, ASTA Pharma AG, Bielefeld, Federal Republic of Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / toxicity*
Dose-Response Relationship, Drug
Female
Immunosuppressive Agents / toxicity*
Male
Neoplasms, Experimental / chemically induced*,  mortality
Rats
Rats, Inbred Strains
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Immunosuppressive Agents

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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