Environmental and Molecular Mutagenesis - Legacy Tobacco ...

184 1989 EMS Abstracts- 533
http://legacy.library.ucsf.edu/tid/clb93d00/pdf
Notes IWEVALUATION`bE'IIJM RODENT CYTOGENETIC TEST RESULTS COMPARED TO IN VITRO
TESTS AND CARCIAbGENICITY . Michael 0 . Shelby, Cellular and Genetic Toxicology
Branch, National I te of Environmental Health Sciences, Research Triangle
Park, NC 27709 j~SA
The role of in vivo short-term tests for genetic toxicity in testing schemes
intended to detect potential chemical carcinogens has long been a matter of
discussion . Whether in vivo tests should be part of an initial screening battery
or should only be conducted on chemicals selected by in vitro tests has never been
agreed . Over the past 7 years, a substantial data base of in vivo cytogenetic test
results has been developed through NTP contract studies . Preliminary analyses
have shown that in vivo tests for abearations and SCE perform as well or better
than in vitro tests in identifying carcinogens and in discriminating between carcinogens
and noncarcinogens . Published results and data acquired through NTP for
the mouse micronucleus test are particularly encouraging . It appears that the
micronucleus test, using either bone marrow or blood to score micronucleated
erythrocytes, performs as well or better than tests for aberrations or SCE in bone
marrow cells and at a considerable saving in resources . Use of the micronucleus
test in place of other in vivo cytogenetic assays in initial testing efforts is
under consideration . The results of chromosomal aberration, SCE and micronucleus
tests on a variety of carcinogens and noncarcinogens and the relative performances
of in vivo and in vitro tests will be presented .
534
BACKGROUND FREQUENCY OF HYPERPLOIDY IN BONE MARROW CELLS OF MALE CHINESE HAMSTERS
CW Sheu, JK Lee, CA Arras . RL Jones and KS Lavappa, CFSAN/FDA, Washington D .C . (USA)
Chinese hamsters, with 22 distinctive individual chromosomes, are an ideal species
for aneuploid analysis . In a series of studies, the hyperploidy frequency in bone
marrow cells of 154 male hamsters was determined . The animals were given a single ip
injection of solvent or a potential aneuploidy-inducing chemical . Ten animals were
used per dose and bone marrow was removed at intervals of 6-96 hr . Slides were coded
and 50-100 metaphases were analyzed per animal . A metaphase with more than 22 chromosomes
was classified as a hyperploid cell, and the data were evaluated using a onetailed
Fisher's Exact test . In three experiments, the frequencies of hyperploid cells
were 0 .43, 0 .91 and 1 .14% for the control groups . The combined controls had 17 hyperploid
cells per 2,656 metaphases prepared from 32 hamsters, giving an average frequency
of 0 .64% . The hyperploidy frequencies of treated groups ranged from 0 .50 to 1 .25%,
and there was no significant increase in any treated group over its concurrent control
with the exception of one group treated with vincristine at 0 .75 mg/kg . The observed
increase was not significant when compared to the pooled controls . The treated groups
when combined had 65 hyperploid cells per 7,355 metaphases from 90 hamsters, giving an
average frequency of 0 .88% ; this value was not significantly different from that of
the combined controls . In a fourth experiment, the hyperploidy frequencies based on
800 metaphases from 8 animals per group were 3 .75% for the controls and 3 .13-4 .52% for
the treated groups . These values were significantly higher than those given above .
The discrepancy appeared to be related to the batch of animals and illustrates the
importance of incorporating concurrent controls in assays for aneuploidy .
535
INDUCTION OF HICR01NCL6I IN RAT BOS6 MARROW BY S6LBCTION CHSHICALS . ! . Shi and T . OnB,
Division of Respiratory Disease Studies, National Institute for ocoupational Safety
and Health . HorBantown, WV (USA)
A large number of chemicals have been tested for the induction of micronuclei in
mouse bone marrow cells . Many of these studies were designed to determine proper
sampling times and peak responses . Such studies and infors,ation, however, are rather
limited for the rat bone marrow cells . Bfforts have been made in our laboratory to
determine the dose and sampling time responses of micronuclei after Sprague Dawley
rats were treated with triethylenem.lamine, mitomycin C, vincristin, and dimathylbensanthracene
by a single intraperitoneal injection . Three concentrations were tested for
each compound . Animals were sacrificed 24, 48 and 72 hrs after chemical treatment .
The procedure of slide preparation and staining followed that of Schmid (Mutation Res .
31 :9, 1975) . The number of micronucleated polychrom.tic erythrocytes among 2000
polychromatic erythrocytes (PC6s) and the ratio of PCB to norsochroastic erythrocytes
were determined for each animal . The results showed that all four compounds caused
micronucleus formations in a dose related manner . The peak response sampling tisw is
dependent on the chemical as well as the concentration of chemical . In all cases .
however, an increase in the micronuclested PCis can be detected 24 hrs after chemical
treatment . These results seem to indicate that two sampling times, 24 and 48 hrs,
would be adequate for the micronucleus assay usin8 rat bone marrow cells .
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