Environmental and Molecular Mutagenesis - Legacy Tobacco ...

62 1989 EMS Abstracts
http://legacy.library.ucsf.edu/tid/clb93d00/pdf
Notes were analyzed for DNA single-strand breakage by alkaline elution . A dose-related
positive response for DNA single-strand breaks was obtained . These results indicate
that difloxacin causes an accumulation of single-strand breaks in hepatocyte DNA . It
is possible that accumulation of DNA single-strand breaks may result from the action
of this drug as a topoisomerase inhibitor, but this accumulation may be unrelated to
the apparently artifactual DDS response .
ATRAZINE AND THE GENOTOXICITY OF ITS METABOLITES
Franekic . J . . G . Hulina . J . Kniewald and M . Alabevic
Faculty of Food Technology and Biotechnology . Zagreb . Yugoslavia
174
Tne aim of our study was to examine genotoxicity of atrazine and its metabolites
deethylatrazine (2-chloro-4-amino-6-isopropylamino-s-triazine) and deisopropylatrazine
(2-chloro-4-ethylamino-6-amino-s-triazine) detected by t .1 .c . and gas chromatography,
and structurally identified by mass speetrometry in the kidney . brain and
liver of male rats treated with atrazine .
Experiments were performed with microbial test-systems with Salmonella t himurium
strains TA100 and TA98 (plate-incorporation assay and preineu a ion met an
with Saccharomyces cerevisiae D7 .
In the plate incorporation assay atrazine was negative in both strains (TA100 and
TA98) : deethylatrazine was positive in strain TA100 and deisopropylatrazine was positive
in strain TA98 . Results of preincubation method indicated that all examined
substances are genotoxic and toxic . In S . cerevisiae D7 only deethylatrazine showed
recombinogenic effect. -
175
FIVE COMPOUNDS WITH ANTIVIRAL ACTIVITY TESTED FOR THEIR RESPECTIVE
GENOTOXIC POTENCIES IN THE DROSOPHILA SOMATIC MUTATION AND
RECOMBINATION TEST (SMART) . H . Frei and F .E. Wiirgler, Institute of
Toxicology, ETH and University of Zurich, Schwerzenbach, Switzerland .
The two potential anti-AIDS drugs azidodeo:ythymidine (AZT) and
dideoxycytidine (DDC) were tested for their respective genotoxicity
in the Somatic Mutation And Recombination Test (SMART) of Drosophila .
Both nucleoside analogs apparently interfere with DNA synthesis since
mutant twin spots (IDtdh and f1ta) as well as single spots (mFih or
fjZ2) were induced in the wing disc cells of animals which were
trans-heterozygous for the two recessive markers . ThA compounds were
fed for 48h to 3rd-instar larvae . Sibs from the same cultures which
were heterozygous for the marker QKh and the recombination-suppressing
balancer-chromosome TM3 allowed to evaluate mutagenicity separately
in the absence of recombination . Overall, AZT was 30-50x less
genotoxic than DDC . With DDC, recombination clearly predominated,
whereas with AZT, recombination was only moderately more frequent
than mutation . Three other antiviral agents, i .e . ribavirin, phosphonoformic
acid, and particularly acyclovir also had stronger genotoxicity
than AZT . Thus, SMART is not only useful for rapid screening,
but also allows to assess genotoxicity quantitatively and to take
into account basically different endpoints .
176
CHARACTERIZATION AND EXPRESSION OF EURARYOTIC GENES REQUIRED FOR NUCLEOTIDE EXCISION
REPAIR :YEAST AS A MDDEL SYSTEM . Errol C . Friedberg, Lee Bardwell, A . Jane Cooper,
Itzik Harosh, Wolfram Siede and Jae-Mahn Song, Department of Pathology, Stanford
University School of Medicine, Stanford, CA 94305 .
In the yeast Saccharomyces cerevisias at least 10 genes are involved in the
removal of bulky base adducts . Five of these (RAD1, RAD2, RAD3, RAD4 and RADIO)
are absolutely required for damage-specific recognition and incision of DNA . These 5
genes have been cloned by phenotypic complementation . Their nucleotide sequences
predict expression of proteins with calculated molecular weights of 126 .2 kDa
(Radl), 117 .7 kDa (Rad2), 89 .7 kDa (Rad3), 87 .1 kDa (Rad4) and 24 .3 kDa (Rad10) . The
cloned genes have been tailo4ed into vectors for overexpression in yeast and E .
coli . The RAD3 gene is multifunctional . In addition to its role in nucleotide
excision repair RAD3 is an essential gene . Furthermore, certain rad3 mutant
alleles confer a phenotype of increased spontaneous mutation and increased mitotic
recombination . Rad3 protein has been purified to apparent homogeneity . The purified
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