Environmental and Molecular Mutagenesis - Legacy Tobacco ...

1989 EMS Abstracts 123
nucleation, micronucleation, chromosome structure or number . To further define the Notes
action of chrysotile asbestos upon human cells, asbestos effects were examined in
cultures of the human lung tumor cell lines A549, Calu-1, KNS62, and A1188 . Asbesto3
induced 50% and 100% cytostasis of HBE cells at treatment concentrations of til ug/cm
and 4 yg/cm , respectively . In contrast, three to thirty-fold higher concentrations
of asbestos were required to inhibit tumor cell growth . Maximal growth inhibition was
cell line dependent and ranged from only 20% to 50% . Asbestos produced only two-fold
elevations of binucleation (spontaneous binucleation rate '% .2X) in HBE, KNS62, and
A1188 cells . In contrast, dose-dependent elevations of binucleation (up to 15-fold)
were observed in cultures of A549 and Calu-1 . These results are consistent with observations
that asbestos amplifies the effects of human lung carcinogens such as
cigarette smoke and suggest that this synergy may in part be mediated by 1) asbestosinduced
inhibition of HBE cell growth that permits clonal expansion of pre-existing
carcinogen-induced lesions and/or 2) enhanced susceptibility of some of these lesions
to asbestos-induced cellular events that facilitate neoplastic progression .
353
ISSUES IN THE EVALUATION OF SHORT-TERM TEST PERFORMANCE AND TESTING STRATEGIES .
Barry H . Margolin, University of North Carolina at Chapel Hill, Chapel Hill, NC .
The formal definitions of statistical independence and dependence are reviewed
within the context of construction of batteries of genetic toxicity assays for
prediction of carcinogenicity . The existing empirical evidence in support of independence
or dependence among assays is examined and the impact of statistical dependence
on carcinogenicity prediction systems is explored in depth . Finally, carcinogenicity
screening policies based upon short-term tests are reviewed and studied for their
sensitivity to assumptions or inferences regarding statistical independence or dependence
among tests .
354
HUMAN SPERM CHROMOSOME COMPLEMENTS, EFFECTS OF DONOR AGE, FREEZING AND SEGREGATION
IN TRANSLOCATION AND INVERSION CARRIERS . Renee H . Martin, Division of Medical
Genetics, Department of Pediatrics, University of Calgary and Medical Genetics
Clinic, Alberta Children's Hospital, Calgary, Alberta, Cpnada T2T 5C7
We have studied the effect of age on the frequency of sperm chromosomal
abnormalities in 30 normal donors, stratified by age into 6 age groups (20-24,
25-29, 30-34, 35-39, 40-44, 45+) . Data from newborns had suggested a possible
increased risk of Down syndrome with paternal age but we found no inereased risk
of disomic sperm with advanced patornal age . In contrast, the frequency of
hyperhaploid (n+l) sperm decreased while the frequency of sperm with structural
chromosomal abnormalities increased with age . To assess the effects of sperm
cryopreservation, ejaculates from 10 normal men were split and studied pre- and
post-freezing . A minimum of 100 sperm karyotypes were studied for each donor .
There was no significant difference in the frequency of numerical chromosomal
abnormalities (using a conservative estimate of aneuploidy, 2 x hyperhaploid sperm)
or structural chromosomal abnormalities before and after freezing . There was no
evidence for donor heterogeneity . The sex ratios were also not, affected by
cryopreservation and did not differ significantly from 50% . Studies on 23 men
with constitutional chromosomal abnormalities have demonstrated dramatic variations
in the frequency of chromosomally unbalanced sperm from 0% to 77% . This information
is useful in elucidating basic principles of how rearranged chromosomes segregate
during meiosis and also in providing more accurate genetic counselling for these
men .
355
MUTAGENICITY OF NITROARENES BY NEW TESTER STRAINS, TA100/PY0216, TA100/PY0219, TA98/PYO
216 AND TA98/PYG219 . H . Matsushita, 0 . Endo, H . Katsushita,Jr ., M . Kochizuki, M .
vatanabe, and M . Ishidate, Jr ., National Institute of Public Health, Kinato-ku, Tokyo,
(Japan), Eyoriteu College of Pharmacy, Minato-ku, Tokyo (Japan), and National Institute
of Hygienic Sciences, Setagaya-ku, Tokyo (Japan) . Mutagenicity of nitroarenes, potent
environmental mutagene, was tested by new tester strains, Salmonella typhimurium TA
100/PYG216, TA100/PYG219, TA98/PYG216 and TA98/PY0219 as well as the parent strains,
where TA100/PYG216 and TA98/PYG216 have nitroreductase activity and TA100/PY0219 and TA
98/PYG219 have acetyltraneferase activity . Mutagenicity test was carried out by the
pre-incubation method in the presence and absence of S9 mix . Nitroarenes tested were
21 nitro-derivatives of benzene, biphenyl, naphthalene, anthracene, fluorene and pyrene,
in which 8 dinitropyrenes were included . The mutagenic activity was generally higher
in the absence of S9 mix than in the presence of S9 mix for all ∎trains tested . Mutagenic
activity of each nitroarene was generally in the order of TA100/PYG219, TA100/PYG
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