Environmental and Molecular Mutagenesis - Legacy Tobacco ...

247
GESVMXICITY OF MRGANIC MEFiLURH
HEIMI, S . ; EIrSFEFII, M. ; EL-ZYAT H . & M76TAFA M.H . Institute of Graduate Studies
and FEsearch, University of Alexandria, A exa a, Egypt .
Genotoxic effects of HgC1 were tested using a battery of tests . In Vicia faba
the predaminant cytogenetic iffects in msiosis ware the formntion of ~~i,
structural chranoscme aberrations, and abnormal ctuamsc :ne distribution . In
Saccharanyces oerevisiae, strains were different in their sensitivity to HgC1 , the
nor JD strain was 4 and 1 .4 ppn when ex.oosure was for 3 and 5 hours res~ectively,
Qe the ID5p values for strain D7 were 1 .4 a,rri 0 .6 pZ m. Log-phase cells were more
sensitive th3n those of stationary phase . Mitotic gene conversion at HIS4 locus in
strain JD1 and TRP5 locus in strain D7 was suppressed by HgC1 . In AsMElus imnersus
(Pasadena strains the older the strain the more seensitive R was to HgCr'-CUFUrrg
in distilled water, oomplete liquid , axrl cortQlete solid media supplementW with HgC12
gave different results . Meiotic gene eonversion frequency in + x m crosses was not
affected, only direction of eonversias showed significant change in the favour of
wildtype allele . It was proposed that HgCl influenced mis-match repair mechanism
rather than hybrid DNA formation freduenc .y? However, HgCl increased crossing-over
frequency - except at 1 pfm - significantly. ZWo hypothe2s were proposed to explain
such effect :one is based on the fate of half-chiasmata and their resolution, the
other eonsiders the physical arrangement of chranatids . With respect to forward
mutation frequency, HgC1 significantly lowered the spontaneous frequency of asoospore
colour mutations . Probab~y, the inhibition of enzymes involved in the repair of
premutational lesions by FigC12 caused such reduction .
248
EFFECT OF PHENOLIC ANTIOXIDANTS ON BENZO(A)PYRENE METABOLISM, GENOTOXICI-
TY AND ITS METABOLITES BINDING TO BACTERIAL DNA IN SOS CHROMOTEST .
E .E . Hennig, K .K . Demkowicz-DobrzaAski, and L . Dock, Medical Academy,
02-097 Warsaw (Poland), and The National Institute of Environmental Medicine,
S-104 01 Stockholm (Sweden)
The effect of butylated hydroxyanisole (BHA) and butylated hydroxytoluene
(BHT) has been studied on benzo(a)pyrene (BP) metabolism, .genotoxicity
and BP metabolites binding to bacterial DNA . BP activation has been
performed using S9 fractions from the liver of mice fed a diet containing
BHA or BHT . Both BHA and BHT treatment slightly enhanced total BP metabolism
and markedly increased water-soluble BP nyetabolites formation as was
indicated by the estimation of the distribution of organic extractable
and water-soluble metabolites formed in the presence of S9 fractions . The
HPLC analysis of BP metabolic profile, in the presence of antioxidantsmodified
fractions, shows significant decrease of 9-hydroxyBP formation .
The bacterial test SOS Chromotest was used to study the genotoxicity of
BP . Formation of BP metabolite adducts in Escherichia coli DNA was analysed
by HPLC procedure . There was indicated a strong inhibition of BP genotoxicity
when the S9 fraction from BHT-fed mice was used for BP activation
. BHA had only a moderate, not significant, inhibitory effect . Our
results indicate that there existed a clear correlation between antioxidants
effect on BP genotoxicity and total BP metabolites binding to bacterial
DNA .
249
STRUCTURE-ACTIVITY RELATIONSHIPS INVOLVED IN THE GENOTOXICITY OF ANALOGS OF PYRVINIUM
IN YEAST AND BACTERIA . U .G .G . Hennig and R .C . von Borstel, Department of Genetics .
University of Alberta, Edmonton, Alberta (Canada) T6G 2E9
The structural requirements for the mutagenic action of pyrvlniue were investigated
with structural analogs . The genotoxicity of these analogs was studied in diploid (D5
and 07) and haploil (XV1B5-14C, XY718-1A, and •1854-1A) strains of Saooharomyoee
cereviaiae . Substitution with a methyl group at the 6-position of pyrviniuln did not
affect the mutagenicity ; the 6-methyl-analog induced frameshift and base-substitution
mutations just as readily . However, the 6-methyl-analog induced both transitions and
transversions, whereas pyrvinium induced only transitions . With the 6-chloro-analog,
the toxicity and mutagenicity were diminished but detectable levels of frameshifts and
transitions were observed . Pyrvinium and the 6-chloro-analog induced frameshifts and
transitions, whereas the 6-methyl-analog induced frameshifts, transitions, and
transversions . The hydroxylation of the methyl-substituent of the 6-methyl-analog
probably results in a mutagen that is as active as pyrvlniun itself . A second DNA
binding site is the cationic site at the methylated ring nitrogen of pyrvinium . This
is evident fram the diminished, yet not abolished, genotoxicity of the chloro-analog .
A methyl- or dimethylamino-substituent at the 6-position and the cationic site at the
methylated ring nitrogen are required for mutagenic activity . The reversion spectra
for SaZmoneLLa typh{muri.um (strains TA97, 98, 100, and 102) indicate that the chloroand
methyl-analogs are mutagenic in all strains (-S9 and +S9) . Pyrvinium pamoate and
pyrviniun iodide are frameshift mutagens (-S9 and +S9) but activation is required for
them to induce base-substitution mutations . (Research supported by NHRDP and AHFMR) .
http://legacy.library.ucsf.edu/tid/clb93d00/pdf
1989 EMS Abstracts 87
Notes