Environmental and Molecular Mutagenesis - Legacy Tobacco ...

294 1989 EMS Abstracts
THE PERSISTENCE OF DICENTRIC CHROMOSOMES IN MURINE SPLENIC AND PERIPHERAL BLOOD Notes
LYMPHOCYTES (PBLs) FOLLOWING IN VIVO ry-IRRADIATION . A .D . K1lgermanl E .C . Halperin2
G .L . Erexson3, and G . Honor42 . lU .S . Environmental Protection Agency, Research
Triangle Park, NC ; 2Duke University Medical Center, Durham, NC ; 3Environmental Health
Research and Testing, Inc ., Research Triangle Park, NC .
In developing extrapolation models for human genetic toxicology studies, it is
important to determine the persistence of the damage in the target cells in both the
human and the animal model . The persistence of lesions is primarily determined by
three processes : DNA repair, the rate of cell cycling, and cell lifespan . In this
study, we determined the persistence of dicentric chromosomes with paired fragments in
splenic lymphocytes and PBLs following y-radiation as a measure of the lifespan of
these target cells . Thirty-six male C57B1/6 mice were whole-body ry-irradiated (WBI)
with 3 Gy using a linear accelerator . Blood and spleens were removed from each of 4
mice within 30 min, and then on days 1,3,7,14,28,56, and 112 after WBI . Both B- and Tlymphocytes
from the spleen and T-lymphocytes from the peripheral blood were cultured
for one cell division for analysis of dicentric prevalence . Decay curves for Tlymphocytes
from the spleen and peripheral blood were similar describing the average
lifespan of a T-cell to be 25 and 18 days, respectively . The shape of the B-cell decay
curve was very different from those of the T-cells, showing little change from day 0
through 7(40X of the cells contain at least one dicentric with a fragment) . At day
14, 90% of the cells with dicentrics have disappeared . However, for both B- and Tlymphocytes,
there exists a small population (approximately 2%) of long-lived cells 112
days after WBI that contain dicentrics with fragments . [This abstract does not ratl .ot 6vA policyl
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COMPARING THE STRUCTURAL DETERMINANTS OF MUTAGENICITY IN THE GENE TOX AND NATIONAL
TOXICOLOGY PROGRAM DATA BASES . Gilles Klopman and Herbert S . Rosenkranz, Departments
of Chemistry and Environmental Health Sciences, Case Western Reserve University,
Cleveland, Ohio 44106. `
The Gene-Tox (GT) and National Toxicology Program (NTP) Salmonella mutagenieity
data bases have been widely analyzed with respect to their performances as predictors
of carcinogenicity . The two data bases differ greatly : in GT, mutagens predominate
(80%) prevalence), and 88% of the subgroup also tested for carcinogenicity, was
carcinogenic . In NTP, on the other hand, only 54% of the ehemicals are mutagens . The
prevalence of carcinogens is 67% but 40% of them are not mutagenic . The two data sets
were each analyzed by CASE, the Computer Automated Structure Evaluation method . It
was found that there was a highly significant overlap among the structural
determinants responsible for the mutagenicity in each data set, even though there was
insignificant overlap of the chemicals in GT and NTP .
These findings indicate that each data set can be used for mechanistic studies
and that in future studies they can be merged . The results, using two independently
obtained data bases, prove that there is a unique structural basis for mutagenicity .
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DE"rERmnoTION OF DAlfAGFNIC EFFFICiS IN LIVER .S, SPIFMr INfESmaI. CZxA'FSRS, BzACD SERA
AIID URIHE OF NIItIDA7AIE TRF7ITID fYQCE WITH E . OOf,I K-12 STRAINS
Siegfried Knascdiller
Institut of Experimental Carx :er Research, University of Innslaruck
Fritz-Pregl-StraBe 3/VII, 6020 Innsbruck, AUSTRIA
Intrasanguirteous Host Mediated Assays were performed to ereasure the induction of valine
and nalidixic acid resistant imutants in E .eoli K-12 oslls reeovered fran livers and
spleens of mice treated orally with the antischistoeanal drug Niridazole (dose range
500 - 125 mg/bo8y weight. Following an exposese tine of 180 minr a substantial dose
dependent mutagenic respalse was fotimd in both or+gans with tYte nitr+oz'eductase pa'oficient
parental strain E .eoli K-12 343/113 whereas with a niridazole nitrodreductase
deficient derivative 343/113 NIR 200 (which resists the toocic action of 200 pg Niridazole
per ml agar median), no c]ear sutagenic effects were detectable under identical
experimental ootditions . In additienr urine samples, extracts of intestinal eontents
and blood sera of niridazole treated animals were tested in liquid suspension assays•
with the reductase proficient strain pronounced activities were fatald in all camsr
whereas with the reductase deficient strain, positive results were restricted to experiments
with urine smnples . These latter findings stx3qest that nutaqenio nletabolites
formed by nkTmlalian enzymes and/oz nitsnreductiea by intestinal mieroorqattisire at ooncentratiens
wich are to low to enable their detectien under the present in vivo oonditicns
are concentrated by ultrafiltration and excreted via the renal system .
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