Environmental and Molecular Mutagenesis - Legacy Tobacco ...

126 1989 EMS Abstracts
http://legacy.library.ucsf.edu/tid/clb93d00/pdf
Notes have shown that reconstitution experiments utilizing purified rabbit cytochrome P-
450 isozymea that all three xenobiotics are preferentially metabolized by isozyme
3b (IIC3) a constitutive form thus far found only in rabbits . The ability of Pb to
induce the metabolism of 1-NP, 3-NF and N was also anticipated since Ssozyme 2(II
81) one of the major forms induoed by phenobarbital also exhibited significant
activity with these compounds in reconstitution studies . Signifioant metabolism of
all three xenobiotios occurred in pulmonary miorosomes . Since environmental
exposure to these three xenoblotlos will most likely be via inhalatlon and that
common pathways of C-oxidation are involved in their metabolism, significant
interactions between the three can be expected when present concurrently in complex
mixtures . Supported in part by grants ES 03648 and AA 07219 .
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COMPARISON OF-MUTAGENICITY OF TEN CHEMICAL MUTAGENS WITH THE SALMONELLA
(AMES) ASSAY, UMU TEST, AND SOS CHROMOTEST . Audrey E . McDaniels,
Antolin L . Reyes, and Larry J . Wymer, U .S . Environmental Protection
Agency, Environmental Monitoring Systems Laboratory, Microbiology
Research Division, Cincinnati, Ohio 45268 .
With the greater number of environmental samples examined each year
for mutagens, there is an increased need for methods that are less time
consuming yet do not sacrifice sensitivity or reproducibility . Two alternative
methods to the well established Ames test are the Umu test and
SOS chromotest . These two colorimetric assays are based on production
of B-galactosidase in response to DNA damage . The three methods were compared
in 5 independent experiments . Dose response curves were obtained
using 10 chemical mutagens representing 6 different classes of mutagens .
Sensitivities, expressed as minimum significant doses (MSD), and precisions
were also measured . Ames test MSDa ranged from 0 .002 pg to 2 .65 pg
per plate for Salmonella ~ty himuri~um strains TA100 and TA98 . SOS chromotest
MSDs rangedom ~0 2 p~ g to 6 . .9 pg per assay, and Umu test MSDa
from 0 .005 pg to 0 .39 pg per assay . The range of precisions among the
assays for all mutagens extended from 0 .07 to 0 .19 . The results of this
study indicated the Umu test was either equivalent to or significantly
better than the Ames test in sensitivity and precision for all of the
chemicals examined . The SOS chromotest presented toxicity and solubility
problems not observed with the Ames and Umu tests .
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CYTOGENETIC EVALUATION OF THE IN VIVO GENOTOEICITY OF THREE QUINOLINE COMPOUNDS
A .F . McFea and K .W . Lowe, Oak Ridge Associated Universities, Oak Ridge, TN (USA)
Quinoline-derived compounds are widely used in medicine and industry as antiseptics,
solvents, dyes, and components of various chemical processes . In vitro assays of their
genotoxicity have yielded varying indications of potency, and few studies of their in
vivo activity have been reported . Ye implanted male 86C3F1 aice with BrdU tablets and
1 hr later gave injections of quinoline or 8-bydroxyquinoline in corn oil solution, or
4-nitroquinoline-l-oxide (4NQ0)dissolved in DMSO . Each was tested at its maximum
tolerated dose (MTD) and at 0 .5 and 0 .25 MTD . Chromosome aberrations were scored in 50
first-division metaphases from each of 8 mice per dose level at 17 hr post-treatment,
and SCEs in 25 second-division metaphases from 4 mice per level at 23 br . Compounds
showing no effect on an endpoint were further tested for aberrations at 36 hr, and for
SCEs at 42 hr . Unusually low control values resulted in a significant p-value for
aberration induction by quinoline at 17 hr ; however, a repeat study showed no effect .
Quinoline also showed no effect on aberration levels at 36 hr, no elevation of SCEs at
either 23 or 42 br, and no indication of an effect on the rate of csll proliferation .
8-bydroxyquinoline was also without effect on either aberrations or SCEs at any
post-treatment time, although a modest depression of call proliferation rates occurred
at the higher dose levels . 4NQO was a very potent inducer of both aberrations and
SCEs, causing a significant increase in aberration rate at 30mg/kg, and in SCE at
15mg/kg ; a depression of cell proliferation was also evident . Both quinoline and
8-hydroxyquinoline seea to be without in vivo genotoxic activity, whereas 4NQO retains
a significant potency under in vivo conditions . Supported by NIEHS Interagency
Agreement Y01-ES-20100 and DOE/ORAU Contract DE-ACG5-760R00033 .
IN DITRO MAMMALIAN CELL CENOTOXICITY ASSAYS : THEIR USE AND INTERPRETATION .
Douglas McGregor, Dept . of Toxicology and Safety Assessment, Soehringer
Ingelheim Pharmaceuticals, Inc ., Ridgefield, CT 06877, USA .
To address the interest in identifying all aspects of genetic toxicity and its
relevance to Man, more than 100 different test methods have been developed .
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