Environmental and Molecular Mutagenesis - Legacy Tobacco ...

70 1989 EMS Abstracts
Notes
http://legacy.library.ucsf.edu/tid/clb93d00/pdf
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LIVER PROTEIN EXPRESSION IN FETAL MICE HOMOZYGOUS OR RETEROZYGOUS FOR CHROMOSOMAL
DELETIONS AROUND THE ALBINO LOCUS . C .B .Giosetti, M .A .Geazsell, S .L .Tollaksen, and
S .Gluecksohn-Waelsch, Argonne National Laboratory, Argonne, IL (USA) and Albert
Einstein College of Medicine, Bronx, NY (USA)
Liver protein expression was examined in fetal mice homozygous or heterozygoua
for the c3N or c14CoS deletions in the albino locus region of chromosome 7 to identify
apecific gene products that correlate with the dedeted ene s,~ ences . Liver
proteins from vildtype (ceh/cch)~ heterosygous (co /c3 or cc14 ~), and homozygous
(c3H/c3H or c1~'CoS/c14C0S) fetal mice (18/19 days gestation) were separated by
two-dimensional electrophoresis (2DE) . The Coomassie Blue-stained protein patterns
were screened for both qualitative and quantitative protein differences by using the
Tycho analysis system . In the 2DE patterns from c3H homozygotes, 20 proteins were
missing that were present in equal abundance in patterns of c3H heterosygous and
h4~o~gous wildtype littermates . However, the same 20 proteins were present in the
C1 homozygotes . In addition to the 20 qualitative protein differences, five
proteins were effected quantitatively in the c3H homozygotes (four decreased and one
increased in expression) relative to both heterosygous and homozygous vitdtype
littermates . The identity of quantitative expression in deletion heterozygotes and
wildtype homozygotes supports previous interpretations of experimental findings
suggesting that the albino deletions involve loss of one or more regulatory genes .
This work was supported by the U .S .DOE, ONER, contract W-31-109-ENG-38, NIH grant
GM27250, American Cancer Society grant CD38 .
COMPARATIVE MUTAGENICITY AND GENOTOXICITY OF THE ANTIPARASITIC DRUGS .
MEBENDAZOLE . FLUBENDAZOLE AND AN OXIME DERIVATIVE OF FLUBENDAZOLE
A .K . Girl, S . Osorio, J .E . Sinsheimer, D .S . Mise and L .B . Townsend .
College of Pharmacy . University of Michigan . Ann Arbor . MI 48109 . USA .
As part of a program to develop compounds with macrofilaricidal activity . we
have tested the ∎utagenicity in Salmonella, and the In vivo genotoxicity to
bone- marrow cells in ∎ice of the commercially available anthelaintic drugs
Mebendazole and Flubendazole as well as an oxiae prodrug of Flubendazole . This
information was sought to develop a base line for the further preparation of
∎ore efficient .acrofilaricidal compounds without eenotoxiclty . Mutagenicity
was established only for TA 98 with the presence of $9 at high doses for
Mebendazole and at lower levels for the oxime . Mutagenicity was not observed
for Flubendazole under the same conditions . A dose related increase in sister
chroaatid exchanges (SCE) was found In vivo for Mebendazole and Flubendazole .
There were comparable significant (pNPO>NPGEtTCPO> control . When the genotoxic
effects of two of their metabolic precursors, 1-allylnaphthalene (AN) and
trichloropropylene (TCP) were also carried out In vivo . AN was genotoxic in bone
marrow but not TCP . The ∎uch shorter half life of TCPO is a factor in
explaining the lower SCE and CA results than would be predicted by chemical
alkylation rates or by the preincubation version of the Ames test . DNA strand
breaks in liver were used as a test requiring less In vivo exposure ti .e for a
genotoxicity comparison of the four epoxides and the two precursors . A
significant increase in x of unwound DNA was observed for all the compounds
except AN at high doses . TCPO, the least gsnotoxic in bone marrow . Is indicated
to have the greatest liver toxicity after 4 b exposure while NOE shows the most
toxicity after 6 h . Supported by grant RO1 ES0334S . NIENB .
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