Environmental and Molecular Mutagenesis - Legacy Tobacco ...

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1989 EMS Abstracts
CHLOROPHYLLIN IS AN ANTIMITAGEN IN DROSOPflIIA ItEIANOGASTRRf Notes
Dra . R . Rodriguez-Arnaiz and S . Zimmering . Universidad Nacional Autonoma de Mexico,
Coyoacan 04510, Mexico, D:f. MEXICO .
In Drosoohila Melanogaster chlorophyllin was tested for its ability to inhibit or
reduce SLRL using the $ggg method and CS males . A brooding scheme of 0-2 and 3-5 days
was employed . Two groups of experiments were run . First, males were fed with DMN (75ppm
for 48 hours) and then they were injected with a solution of 0 .5% chlorophyllin sodium
salt in 5% sucrose solution . A second group of males was injected with the 0 .5% solution
of chlorophyllin and the fed DMN at 75ppm for 48 hours . The negative control were only
injected with chlorophyllin and the positive control only fed DMN . The SLRLT was run as
usual . Results obtained show a decrease in the number and proportion of sex-linked
recessive lethals in groups treated with DI4d+chlorophyllin and chlorophyllin+DMN .
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Antomatic Evaluation and Comparison of Micronuclel Frequencies in Bone Marrow
and in Peripheral Blood of Rats Treated with Various Model Clastogens .
F. Romagna and A . Papapetropoulos . Drug Safety Assessment/fosieology, Sandoz
Ltd., CH-4002 Basle, Switzerland.
A new technology is presented which offers high quality slides suitable for fullyautomated
micronuclei scoring by computerized image analysis and In addition, allows
the enrichment of immature peripheral blood erythrocytes by using step•gradient
centrifugation . Repeated dosing of rats for four consecutive days led to a steady state
level of micronuclei Induction In bone marrow as well as in peripheral blood. In the
latter, maximal response was delayed. In contrast, no elevated micronuclei frequencies
could be seen in the mature erythrocyte population Indicating that micronuelelIn this
cell compartiment were mainly removed by spleenic function . Theae results are In
contrast to observations made in several mouse strains, where accumulation of
micronuclei in mature erythrocytea does occur. Our data clearly demonstrated that the
immature erythrocyte population of rat peripheral blood Is a highly sensitive system
for micronucleus testing and that a steady state level with maximal drug response can
be achieved by using a multiple dose regimen . It is hoped that this study may encourage
further evaluation of the rat peripheral blood micronucleus test fdr routine purposes
in genetic toxicology .
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GENOTOXIC AND NON-GENOTOXIC CARCINOGENS CAN BE IDENTIFIED AND PREDICTED BY CASE, AN
ARTIFICIAL INTELLIGENCE SYSTEM . Herbert S . Rosenkranz, Dept . of Environmental Health
Sciences, School of Medicine, Case Western Reserve Univ ., Cleveland, Ohio 44106
Analysis of short-term test and animal carcinogenicity results indicates that
there are genotoxic carcinogens (GC) which are characterized by the ability to induce
cancers in mice and rats, at multiple sites and in both genders, and there are nongenotoxic
carcinogens (NGC) which are species- and site-specifio and may be
restricted to a single gender . NGCs cannot be differentiated from non-genotoxic noncarcinogens
by short-term teats or "structural alerts" . CASE, the Computer Automated
Structure Evaluation system Was applied to this situation and a number of findings
were made :
1 . CASE was successful in handling non-congeneric SalmoneUamutagenieity data bases .
The structural determinants (biophores) identified could be used to prediet
mutagenicity and to study mechanisms of mutagenicity . In spite of many differences
in the composition of the NTP and Gene-Tox data bases, the same major biophores were
identified in both .
2 . Analysis of the NTP carcinogenicity data base revealed that CASE was highly
effective in classifying carcinogens and non-oaroinogens (sensitivity, 1,00 ;
specificity, >0 .86) . Additionally, CASE allowed the recognition of NGCs based upon
unique structural features . CASE identified three types of oaroirwgen-speoifio
biophores : (a) those' specific for GCs (primarily eleotrophilio or potentially
electrophilic biophores) ; (b) NGC-specifio biophorea and (a) non-eleotrophilio
biophores shared by some GCs and NGCa . These findings reveal an unexpected structural
commonality among NGCs and permits a systematic study of the basis of their action .
http://legacy.library.ucsf.edu/tid/clb93d00/pdf
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