Document Detail


Genotoxicity of the cancer chemopreventive drug candidates CP-31398, SHetA2, and phospho-ibuprofen.
MedLine Citation:
PMID:  22498038     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The genotoxic activities of three cancer chemopreventive drug candidates, CP-31398 (a cell permeable styrylquinazoline p53 modulator), SHetA2 (a flexible heteroarotinoid), and phospho-ibuprofen (PI, a derivative of ibuprofen) were tested. None of the compounds were mutagenic in the Salmonella/Escherichia coli/microsome plate incorporation test. CP-31398 and SHetA2 did not induce chromosomal aberrations (CA) in Chinese hamster ovary (CHO) cells, either in the presence or absence of rat hepatic S9 (S9). PI induced CA in CHO cells, but only in the presence of S9. PI, its parent compound ibuprofen, and its moiety diethoxyphosphoryloxybutyl alcohol (DEPBA) were tested for CA and micronuclei (MN) in CHO cells in the presence of S9. PI induced CA as well as MN, both kinetochore-positive (Kin+) and -negative (Kin-), in the presence of S9 at ≤100μg/ml. Ibuprofen was negative for CA, positive for MN with Kin+ at 250μg/ml, and positive for MN with Kin- at 125 and 250μg/ml. DEPBA induced neither CA nor MN at ≤5000μg/ml. The induction of chromosomal damage in PI-treated CHO cells in the presence of S9 may be due to its metabolites. None of the compounds were genotoxic, in the presence or absence of S9, in the GADD45α-GFP Human GreenScreen assay and none induced MN in mouse bone marrow erythrocytes.
Authors:
Rupa S Doppalapudi; Edward S Riccio; Zoe Davis; Sean Menda; Abraham Wang; Nicholas Du; Carol Green; Levy Kopelovich; Chinthalapally V Rao; Doris M Benbrook; Izet M Kapetanovic
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-04-10
Journal Detail:
Title:  Mutation research     Volume:  746     ISSN:  0027-5107     ISO Abbreviation:  Mutat. Res.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-05-01     Completed Date:  2012-07-19     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  0400763     Medline TA:  Mutat Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  78-88     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier B.V. All rights reserved.
Affiliation:
SRI International, Biosciences Division, Menlo Park, CA 94025, USA. rupa.doppalapudi@sri.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Anticarcinogenic Agents / toxicity*
CHO Cells
Chromans / toxicity*
Chromosome Aberrations
Cricetinae
Cricetulus
DNA Damage / drug effects*
Dose-Response Relationship, Drug
Female
Humans
Ibuprofen / analogs & derivatives*,  toxicity
Mice
Micronucleus Tests
Mutagenicity Tests / methods
Mutagens / toxicity*
Organophosphates / toxicity*
Pyrimidines / toxicity*
Rats
Rats, Inbred F344
Salmonella typhimurium / genetics
Thiones / toxicity*
Grant Support
ID/Acronym/Agency:
HHSN26120043305C//PHS HHS; N01CN43305/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/(((4-nitrophenyl)amino)(2,2,4,4-tetramethyl thiochroman-6-yl)amino) methane-1-thione; 0/2-(4-isobutylphenyl)propionic acid 4-(diethoxyphosphoryloxy)butyl ester; 0/Anticarcinogenic Agents; 0/CP 31398; 0/Chromans; 0/Mutagens; 0/Organophosphates; 0/Pyrimidines; 0/Thiones; 15687-27-1/Ibuprofen
Comments/Corrections

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