Environmental and Molecular Mutagenesis - Legacy Tobacco ...

;
deletion of his-_3 . In the remaining forced dikaryon, the 5 .9 kb fragment was present
in addition to a 2 .6 kb fpagment . Thus, the latter 3/30 Ad;_39 pdZR mutants probably
resulted from multiple 4obus mutation . Thus, data from these studies demonstrated
that the majority of X-ray-induced mutants classified as presumptive multilocus
deletions by classical genetic tests are actual interstitial deletions .
431
Ai r"'UPIAIDY IN MOUSE 00CYTES AND 0NE-C°L .L ZYGOTf.'S AFfF:R ORAL DOSAGES OF GRIS. .OFULVIN
F .?acchie :rotti,C .Tiveron,F .Marchetti,B .Bassani,Lab .Toxicology,FN'cA Casaccia,Roma,Italy
Griseofulvin (GF) has been characterized as a mitoclastic agent in :namralian cell
cultures probably causing spindle disrL4)tion by inhibition of cmrbination between .nicro
tubules and microtubule associated proteins . Doses of 200, 666, 1332 or 2000 mg per kg
of body weight dissolved in olive oil have been administered by gavage to young superovulated
BC3F1 female mice either at the time of hunan chorionic gonadotrophin (ECG)
injection or 2 h later . Metaphases of secondary oocytes or one-cell zygotes have been
prepared 18 or 42 h (overnight cultivation in colchicine added mediun included) after
HCG respectively . Cytogenetic analysis of secondary oocytes showed that when GF was
given at the same time of ICG a dose-dependent induction of meiotic arrest was observed
without any evidence of aneiploidy in the oocytes which had corrpleted the first meiotic
division . When the same dose (2000 mg per kg) was given 2 h later a reduction by a
factor of 3 .6 of the meiotic arrest was observed, while a preliminary analysis showed
that 23 out of 40 (57 .5 %) analyzed metaphases were aneuploid . Observatims of one-cell
zygotes showed that approximately all the oocytes which had been arrested at the first
meiotic metaphase underwent irregular fertilization and gave rise to polyploid zygotes
or zygotes with an MI or MII arrested female pronucleus . These data suggest the inportance
of treatment time during meiotic progression as a flmction of the way of chemical
adninistration and of the cellular target and mechanism .s of aneuploidy irxSuction .
432
PREDICTING CARCINOGENIC POTENCY : THE USE 0f A BATTERY
OF GENOTOXIC AND ACUTE TOXICITY ASSAY RESULTS
S . Richter Pack
C .C . Travis
Oak Ridge National Laboratory
Recent studies focusing on the ability of short-term mutagenicity assays to
predict the potency of positive carcinogens have found equivocal correlations
between mutagenic potency and cancer potency . The squivocal correlation may be
due to a failure of the short-term tests to account for the ability of some
compounds to act as cancer promoters . It is difficult to assess the extent that
a measure of promotional ability will increase the predictivity of short-term
test batteries since an adequate short-term test for promotion is not available .
We propose using acute toxicity data (LDSO) as a surrogate measure of promotional
activity . The suggested biological basis for this relationship is that tissue
damage and consequent cell proliferation may be a surrogate measure for tumor
promotion . We have found that including an assay for cytotoxicity in a shortterm
test battery results in an increase in cancer potency predictivity to
roughly 0 .84, as opposed to 0 .40 for the Ames test alone .
433
MUTAGENICITY OP THE HUMAN CARCINOGEN TREOSULPBAN IN SALMONELLA . D . A . Pa ano
and E . Zeiger, Cellular and Genetic Toxicology Branch, National Inst tute o
Environmental Health Sciences, Research Triangle Park, NC 27709 (USA)
Treosulphan (TREO) is an alkylating agent that is used for the treatment of
ovarian cancer and has been shown to be a human carcinogen . As part of a
study of the mutagenic effects of human carcinogens, TREO and its hydrolysis
products, diepoxybutane (DEB) and methanesulfonic acid (NSA), vere tested for
mutagenicity in Salmonella . TREO and DEB were direct acting mutagens in
strain TA1535 . TREO induced 116 rev/plate at a dose of 1 .87 umols and DEB
induced 50 rev/plate at 0 .88 umols . The use of a preincubation protocol or
the addition of rat-liver S9 caused a slight enhancement of TREO mutagenicity,
but a decrease in DEB mutagenicity . NSA was not mutagenic or toxic up to 128
http://legacy.library.ucsf.edu/tid/clb93d00/pdf
1989 EMS Abstracts 149
.
Notes