Environmental and Molecular Mutagenesis - Legacy Tobacco ...

66 1989 EMS Abstracts
http://legacy.library.ucsf.edu/tid/clb93d00/pdf
Notes cenlly increased . HI'• also has the sffect of laducing relrugrade infeclion or
urugenital sysles . F.Y enhanced the gassa ray carcisogenieily, thereby
increasing the tumour incidence or the ratio of sa1)gnant to benign tuaosrs .
Mhen added into the sedium, 1iY,fi or P aloae •as able to directty lnduce
matignant transformation of souse esbtyo cetls in vitro . it caa partly explain
the reasan •hy the aajur lyps of tusors ladueed by 8Y in various atralae of
sire ua : qaitr difforeat as a result of observing ihe distribution of
trltialed estradlol receptor cosplexes in various t)ssues and organs by
nutoradlography .
186
HUMAN GENOTOXICITY IN PHOSPHINE-EXPOSED APPLICATORS . V . Garry, T . Danzl, J . Griffith,
R . Nelson, E . Whorton, University of Minnesota, Minneapolis, MN (USA), and U .S . EPA,
Research Triangle Park, NC (USA) .
Fumigation of grain is a world-wide agricultural practice . In this effort, we
examined the health histories of more than 400 persons who may have come in contact
with fumigants and pesticides . We identified a small group of workers who perform
fumigant application . We then undertook an integrated human study of fumigant
applicators exposed to phosphine, one of the most common fumigants . Evidence for
qenotoxicity was expressed in terms of sister chromatid exchanges and chromosome
aberrations in banded and non-banded preparations . These data were coupled with
personal breathing zone sampling for phosphine . As a group, applicators (n-24) show
significantly increased chromosome aberrations compared to control subjects (n-24) .
Workers exposed to phosphine alone (n-9) have increased chromatid gaps/deletions
compared to all other groups . Workers earlier exposed to phosphine or to phosphine
and other pesticides have significantly increased chromosome rearrangements,
including chromosome translocations (11/12) compared to controls (2/10) . Chromosome
breakpoints identified in the exposed workers seem to cluster in certain oncogene
regions of specific chromosomes . In vitro studies of phosphine suggest that
phosphine or a phosphine-generated product(s) crosslinks DNA as studied by alkaline
elution procedures . Further work indicates that the mechanism of qenotoxicity may
be related to peroxidase inhibition .
187
A IL TRDUSTRIAL AND UK PERSPECTIVE ON SHORT TER_M TEQTING .
DG Gatehouse, Genetic and Reproductive Toxicology Department, Glaxo Group Research
Lta ., Ware, Herts .
The appropriate use of short-term tests for the screening of carcinogenic agents
is currently under review . In the UK, the DHSS Committee on Mutagenicity (COM) has
been revising its guidelines with a view to publication later this year . To
compliment this the UKEMS are revising their recommendations for the conduct of the
main categories of short-term tests . In these revisions it is recognised that a
limited number of in vitro tests carried out exhaustively but with a degree of
flexibility is the most effective strategy for priaary screening . Mammalian gene
mutation assays have been retained in the revised DiiSS CON Guidelines, aa some
"unique" mammalian cell mutagens have been identified by the recent R!P study .
However, the credibility of these data is being contested and further studies are
required to resolve this . There is still considerable debate on the role of
short-term in vivo tests ie . confirmatory or screeningt . Their use as screens may
still be essential when complex metabolic activation processes are required . If used
in a confirmatory role, there is accumulating evidence that organ-site specificity
requires that more than one tissue should be examined to eliminate false negative
results . It is possible that species-specificity might also be an important
consideration when designing experimental protocols . Finally the need for an
additional test(s) to detect "aneugenic" agents has still to be decided . Some
potential aneugens may be detectable using the existing assays (eg micronucleus teat
and in vitro cytogenetic assays) . Further validation data are required before any
firm decisions can be made .
188
DATA AND RATIONALE FOR A MODEL THAT EXPLAINS THE VARYING FREQUENCY OF ANEUFLOID CHILDREN
WITH MATERKAL AGE (THE J-SHAPED CURVE) . M .E . Caulden, Radiology Department, University
of Texas Southwestern Medical Center, Dallas, TX 75235
The majority of aneuploid children are born to older women and result from nondisjunction
at first meiotio division in the ovary . What ovarian condition promotes
aneuploidy induction? I propose that it As decreased miorooiroulation around follicles,
leading to deficient 0p supply and a concomitant inorease in C02 and anaerobic produots
such as lactic acid, whioh lower pH . We have found that exposure of somatic cells in
vitro for 1 h, 38°C to C02 or acid medium (pH