Document Detail


Screening for agents inhibiting the mutagenicity of extracts and constituents of tobacco products.
MedLine Citation:
PMID:  7519327     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The aim of this study was to screen for potential agents affecting the mutagenicity of tobacco products. The influence of a number of compounds which have been suggested to be antimutagenic some of which are present in tobacco products, was investigated on the mutagenicity of a cigarette smoke condensate (CSC) and, in some cases, an extract of oral Swedish moist snuff (SNUS), using a screening procedure of the Ames Salmonella/microsome assay (STY). For some of the compounds the V79/hprt mutagenicity assay with benzo[a]pyrene metabolites as mutagens was used to obtain complementary and confirmatory information on mammalian cells. The antimutagens used included two selenium compounds, sodium selenite and ebselen; the flavonoids and polyphenols, ellagic acid, (+)-catechin hydrate, scopoletin, chlorogenic acid and rutin trihydrate; the porphyrin derivatives, bovine hemin, biliverdine dihydrochloride, chlorophyllin and a plant extract containing chlorophyll; the terpenoids, beta-carotene, retinol and a mixture of the two epimers (4R) and (4S) of (1S,2E,6R,7E,11E)-cembra-2,7,11-triene-4,6-diols (CBD); and cyclohexanol and ubiquinone. Screening of antimutagenic activities using the STY involves problems with toxicity. In several cases in this study mutagenicity was decreased below the control level without signs of toxicity in the background growth of bacteria. Since the survival of mutants and slight bacteriostatic effects on the background growth cannot be determined accurately in the STY, a reduction in mutagenicity may simply be due to toxicity. Only in cases where a dose-response curve declines to a level at or above the background and then levels off, can toxicity be excluded. An antimutagenic effect determined using this test system is therefore often not sufficient for classifying a compound as antimutagenic until these findings are confirmed in other test systems and, preferably, the mechanism behind this effect is clarified. The results obtained with the selenium compounds were considered to be inconclusive since the reduction in the mutation rate declined below the background level and might only reflect the toxic effects of these compounds. For ellagic acid an almost complete inhibition of the mutagenicity of CSC and SNUS in STY was indicated. This indication of antimutagenicity was confirmed in V79 cells using two metabolites of the CSC constituent benzo[a]pyrene, i.e., trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene and (+)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-oxy-7,8,9,10- tetrahydrobenzo[a]pyrene (BPDE). Chlorogenic acid and (+)--catechin reduced the mutagenicity of CSC and chlorogenic acid also strongly inhibited SNUS mutagenicity. Scopoletin and rutin trihydrate inhibited the mutagenicity of CSC, but showed confounding effects with SNUS.(ABSTRACT TRUNCATED AT 400 WORDS)
Authors:
L Romert; T Jansson; M Curvall; D Jenssen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Mutation research     Volume:  322     ISSN:  0027-5107     ISO Abbreviation:  Mutat. Res.     Publication Date:  1994 Aug 
Date Detail:
Created Date:  1994-09-01     Completed Date:  1994-09-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0400763     Medline TA:  Mutat Res     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  97-110     Citation Subset:  IM    
Affiliation:
Genotox AB, Stockholm, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Antimutagenic Agents / pharmacology*
Drug Evaluation, Preclinical / methods
Flavonoids / pharmacology
Mutagenicity Tests
Mutation
Plant Extracts / toxicity*
Plants, Toxic*
Porphyrins / pharmacology
Smoke / adverse effects
Sodium Selenite / pharmacology
Terpenes / pharmacology
Tobacco, Smokeless*
Chemical
Reg. No./Substance:
0/Antimutagenic Agents; 0/Flavonoids; 0/Plant Extracts; 0/Porphyrins; 0/Smoke; 0/Terpenes; 10102-18-8/Sodium Selenite

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


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