Environmental and Molecular Mutagenesis - Legacy Tobacco ...

164 1989 EMS Abstracts
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http://legacy.library.ucsf.edu/tid/clb93d00/pdf
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to aromatic amines and 30 controls were exaeined .The clastogenic studies were carried '
out vith micronucleus test on exfoliated cells from the urinary bladder and the careinQ
genicity was evaluated through the cytopathological analysis of these cells . Urinary
bladder cells were recovered by centrifuging the urine and pipetting the asdiASnted eelis
onto microscopic slides .Air-dried-alides were Giemsa-atained to micronuclei analysis and
Papanicolau-stained to cytopathological analysis .Tbe possible correlation between preneoplasic
cells and the frequency of micronuclei is being evaluated,whereas the possible
effects of age,smoking habits,alcobol and coffee drinking are also discussed .The aim of
the study presented here was to verify if a combined application of the micrawleus test
and the cytopathological analysis in exfoliated urothelial cells could be used to identify
population groups of high risk for urinary bladder cancer and to verify the antiinitagenic
and anticarcinogenic 3-carotene supplementation effeet .The potential for this method
to be used for noninvasive monitoring will be discussed .This work was supported by
FINEP, CNPq and ROCHE .
476
CHROMOSOME CHANGES DURING NEOPLASTIC PROGRESSION IN RAT TRACHEAL EPITHELIAL (RTE)
CELLS . K . Rithidech, D . G . Thomassen, and A . L . Brooks, Lovelace Inhalation
Toxicology Research Institute, P .O . Box 5890, Albuquerque, New Mexico 87185 .
Chromosome abnormalities are usually observed in tumor cells . Since it is not
known if these abnormalities are the cause or consequence of tumor development, it is
important to characterize chromosomal changes at all stages of progression . The
purpose of this study was to analyze chromosomal changes in RTE cells at preneoplastic
and neoplastic stages of tumorigenesis . RTE cells were exposed to 6 Gy of X-rays or
N-methyl-N-nitro-N-nitrosoguanidine (MiNG) . Preneoplastic enhanced growth variants
(EGVs), the first recognizable step in tumor progression of RTE cells to neoplasia,
were isolated using a selective medium . Eighteen EGVs were isolated 35 days after
exposure . All EGVa from passage 6 were evaluated for chromosomal changes and were
injected into nude mice to test for their tumoriganicity . Five X-ray-induced ECVs
have been analyzed . Four of the five cell lines were hyparploid and one was
hypoploid . G-banding revealed unique chrosasomal alterations in each EGV . The
specific type of changes were deletions (1q), isochromosomes (9q), translocations
(5 . 12), marker chromosome/, and double minutes . Nost of the hyperploid EGVs possessed
at least one extra copy of chromosome 1 . These results suggest that specific
chromosomal changes can be detected in early stages of carcinogenesis . Cytogenetic
studies of the remaining EGVs and of tumor cells produced in nude mice by these EGVs
are underway . Results from these studies will help determine the role of chromosomal
changet in tumor progression . (Research sponsored by the U .S . Department of Energy's
Office of Health and Environmental Research under Contract No . DE-AC04-76EV01013 .)
477
CTTOGENETIC EVALUATION 0F THE IN VIVO GENOTOXICITT OF SUPERLBTNAL DOSES OF DIOXIN .
S .D . Robertson and A .F . McFee, Oak Ridge Associated Universities, Oak Ridge, TN (USA) .
The halogenated aromatic hydrocarbon, 2,3,7,8-tetrachlorodibanso-p-dioxin has
received considerable attention as a highly toxic environmental pollutant . It !s a
positive carcinogen in some test systems and a potent teratogen . Cytogenetic findings
following various sub-lethal doses have ranged from no observable effect on either
chromosome aberration or SCE induetion to modest but significant ineresses in the
ineidence of aberrations . We administered single intraparitoneal lnjeetions of 250,
500 and 1,000 ug/kg (lOx the acute lethal dose) to ule B6C3F1 mice and scored
chromosome aberrations in marrow cells of 8 aice/treatment 17 hr later, and sister
chromatid exchanges in 4 mice at 23 hr post-treataent . One-tail trend test analyses
of the data indicated no significant change in the level of SCEs= the percent of calls
containing aberrations was significantly incraased by the two lower doses but not the
highest level . Sfnce dioxin is slowly excreted froa liver and fatty tissue storage
and lethality of even very high dosas fs not expressed for about 2 weeks, !t was
meaningful to study longer treatment-to-evaluation times . SCgs among 5 mice per group
showed a significant lncruse (p< .05, t test) at 8 days after 1,000 vg/kg doses, but
not at 2 or 4 days ; however, a repeat trial found no elevation of SCBs at 2, 4, 6, or
8 days . The proportions of polycbro .atic erythrocytes baaring ∎icronucla! in the
marrow of treated ∎ice were not different from controls at 1, 3, or 8 days, but
micronuclei in peripheral blood erythroeytes were elevated at 3 days . We conclude
that significant increases in cytogenetlc lesions are not consistently produced by
superlethal doses of dioxin . Supported by NIRRS Interagency Agreement T01-ES-20100
and DOE/ORAU Contract DE-AC05-760R00033 .
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