| ABSTRACT: |
|
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) |