Environmental and Molecular Mutagenesis - Legacy Tobacco ...

152 1989 EMS Abstracts
Notes
http://legacy.library.ucsf.edu/tid/clb93d00/pdf
439
THE HXPULSIQM OF MICRONUCLAI P~OM POLTCHROMATIC nTTHROClTAS OP MOUSB DONS MAAROp IN
VIVO. J . Parto~ J . Deyers , and M . Carriott . Lilly Research Laboratories, sIT
~flly and Co .'~y;'LTeenfield, IN 46140 .
The mouse micronucleus test is a valuable tool for evaluating in vivo chromosome
damage produced by test articles in polychromatic erythrocytes (PCTj o3-bone marrov .
Compounds that are clastogens, such as cyclophosphamide (CP), induce ∎icronuclei
(MN) that are smaller than MN induced by compounds that are spindle poisons, such as
demecolcine (DE) (Hogstedt and Karlason, Mut . Aes . 1S6t229, 1985/ Tas~.moto and
Kikuchi, Mut . Res . 71s127, 1980) . In vitro studies con ucted by Nito at al . (Mut .
Res . 207 :5, T88)ihoved that siitomyc n and vincristine caused a dose-TepenNint
rnluct3on of MN in mouse cell line L-929 but when the ∎icronucleated cells vere then
treated with cytochalasin B, the rate of ∎icronucleated cells was reduced 31-39X due
to MN extrusion . The eurrent study shows 1) MN are expelled from PCs in vivo and 2)
expulsion is dependent upon ∎icronucleus sise . Male and female CD-1 ml-e : vere given
0 .5, 1, 5, and 10 mg/kg of DE or 100 mg/kg of CP . The bone marrov was harvested 24
and 48 hr after dosing and evaluated for micronucleated PCE . Expelled MN still
attached to the PCE cell surface vere also counted . The clastogen, CP, produced MN
that ranged in size from 0 .5 to 2 .8 ym' with a mean of 1 .5 vm' and no expelled MN
were observed . The spindle poison, Dg, induced ∎icronuclei that ranged in sise from
0 .8 to 7 .9 un' . MN retained within the PCE ranged from 0 .8 to 3 .4 ym' with a mean
of 1 .9 um' while expelled MN ranged from 2 .1 to 7 .9 Ym' with a mean of 4 .3 um' . MN
less than 2 .1 ym' are retained within the PCE and MN greater than 3 .4 ym' are
expelled . MN ranging from 2 .1 to 3 .4 Ym' in size may or may not be extruded .
440
THE U .S . ENVIRONMENTAL PROTECTION AGENCY'S INTEGRATED RISK INFORMATION SYSTEM, J . Patterson,
J . Swartout, R . Schoeny, R . Picardi, U . S . Environmental Protection Agency,
Office of Health and Environmental Assessment, Cincinnati, Ohio and Washington, D .C .
The Integrated Risk Information System (IRIS) is an electronic information system
developed by the U .S . Environmental Protection Agency (EPA) containing data related to
health risk assessment . IRIS is the primary vehicle for communication of chronic
health hazard assessments representing EPA consensua after comprehensive review by
intra-Agency work groups . This work group review includes an examination of the
weight of evidence that an agent is likely to be a human carcinogen as well as a consideration
of the validity of a quantitative risk estimate of carcinogenicity . Quantitative
estimates of potential for noncancer health effects are reviewed by a separate
group . The primary intent of IRIS is to provide guidance to EPA personnel in
making risk management decisions . IRIS contains chemical-specific information in summary
format for over 360 agents . The information is structured to provide a description
of the basis for the hazard assessment and a discussion of the uncertainties in
that assessment . An IRIS chemical file is initiated when consensus is reached on an
assessment for carcinogenic or noncarcinogenic endpoints and contains the summary for
that aseessment . Other information, such as Drinking Water Health Advisories, regulatory
actions, acute toxicity, and physical-chemical properties, is added as available
and as resources permit . IRIS is available to the general public by telecommunications
link with a commercial carrier, and to Public Health Foundation members through
the Public Health Network . Access through the National Library of Medicine's TOXNET
is planned .
441
ANALYSIS OF ELECTROPHORETICALLY DETECTED MUTATIONS IN THE MOUSE, AND COMPARISON OF THE
ELECTROPHORETIC AND SPECIFIC LOCUS MUTATION RESPONSE .
J . Peters and S .T . 8a11, N .R .C . Radiobioloqy Unit, Chilton, Didcot, Oxon OXII 0RD (UK)
Mutations occurring in mouse spermatogonial stem cells after exposure to
ethylnitrosourea (ENU) or X-rays have been scored, both by the visible specific locus
test and an electrophoretic test . One aim of the experiment was to compare mutation
rates found by each method, and a second aim was to investigate the characteristics of
the induced mutations . Significant differences in mutation rates per locus for
recessive visible and electrophoretically detectable markers have not been found yet .
Five independent null mutations of glucose phosphate iso .erase-1 were discovered
among the offspring of mice treated with 250 mq/ky ENU . Heterosyyotes are fully
viable and fertile, but homozygotes are not known . One homoayqote dies at about
8 .5 days oost coitum (West et al ., in prep .) . Each mutation results in complete loss
of gene product in all adult tissue~i t¢~ted, as judged by quantitative assay and
electrophoresis, except one, Goi-lsD-mltl . This determines a polypeptide which can be
found only in adult testis, and embryonic stages . Another mutant allele Gui-1sh:au
also codes for a polypeptide which is only seen in embryos . Possibly the mutant
polypeptides are unstable, and thus can be detected only in rapidly dividing tissues .
Molecular analysis by Southern blotting has failed to show 4ifferences between DNA
from the mutants and from the wild types goi-tsa and Goi-ts . These findings are in
agreement with the suggestion that ENU induced mutations are mainly intragenic
changes .
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