Environmental and Molecular Mutagenesis - Legacy Tobacco ...

204 1989 EMS Abstracts
Notes ,
http://legacy.library.ucsf.edu/tid/clb93d00/pdf
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r sex, and race~nf3uences were also investigated for their effects on SCE . A
significant (p < 0 .001) SCE age effect was observed, with SCE frequency increasing
with age .- A a?l,gniftsnt (p < 0 .008) SCE sex effect was also observed, with average
female SCE (8 .76 t 0 .26) higher than the average male SCE (7 .85 t 0 .23) . However, no
significant (p > 0 .94) SCE race effect was detected, although the SCE race * smoking
interaction was significant (p < 0 .01) . Urinary cotinine was determined to be highly
correlated (r - 0 .70) with the number of cigarettes smoked by the children's parents,
and was used as an estimator of the actual amount of smoke inhaled by the children .
This continuing study is presently investigating the role of ANF as a potentiator of
SCE induction in non-smoking, passively smoking, and actively smoking young adults,
and is also using cotinine as an indicator of cumulative smoke exposure for each
subject .
592
ACETYLATION AND ACTIVATION OF 2-AMINO-3,8-DRAUCHYLIIIMAZO[4,5-f]QU1NOXALINE
(MeIQx) TO DNA REACTIVE SPECIES IN SALMONELLA BACTERIA . K . W . Turteltaub, B. E.
Watkins, and J. S. Felton, Biomedical Sciences Division, Lawrence Livermore National Laboratory, P .O.
Box 5507, Livermore, CA 94550 .
The aminoimidoazaarenes (AIAs), a group of heterocyclic amines found in cooked meat, require
metabolic activation to express genotoxicity in a number of in vitro assays, including the Arnes/SalmoneUa
test. The AlAs are mutagenic to Salmonella strains TA98 and TA98NR (nitroreductase deficient) ; but not
to TA98/1,8DNP6 (acetyltransferase deficient), suggesting a requirement for the O-acetyltransferase .
Asan et al. (Carcino enesis, 1987, 8 :1589) have found DNA adducts In Salmonella strains exposed to
the quinoline AIA, IQ . We examined DNA adducts generated in Salmonella following exposure to 2amino-3,8-dimethylimidazo[4,5-f)quinoxaline
(MeIQx) by 32P-posalabeling to access the role of bacterial
acetylation in the activation of one of the quinoxaline AlAs. DNA was isolated from Salmonella TA98,
TA98NR, and TA98/1,8DNP6 foUowing exposure to MeIQx, in the presence of Aroclor-induced mouseliver
microsomes, for 4 hr . Four adducts were found in Salmonella TA98 and TA98NR . The adducts
formed in these strains were judged to be idendcal by eoo-chromatography . No significant difference was
found in adduct frequencies between these two strains . The same 4 adducts were also detected in
Salmonella strain TA98/1,gDNP6 but at significantly lower levels . Synthetic azido-MelQx was reacted
with calf thymus DNA and produced identical adduct profiles to Salmonella DNA as did mice given
MeIQx . These data support the belief that formation of an N-acetoxy AIA intermediate is required to
generated a DNA-reactive species. These data also support the hypo thesis that a single pathway,
independent of species, is responsible for the generation of an ekctrophilic (DNA-reacdve) AIA
(Work preformed under the auspices of the U .S . DOE by the LLNL under contract No. W-7405-F~8
and supported by EAG NIEHS 222Y01-ES-10063).
593
FSTABL•ISHED OR PRIMARY CELL LINES FOR CYTOGEHETIC TESTS?
DJ Tweats and DG Gatehouse, Glaxo Group Research Ltd ., Ware, Herts, England .
When choosing on a cell line for cytogenetic tssts, investigators take into
account the degree of validation ; chromosome stability (in terms of amoku of
chromosomes) ; low spontaneous aberration frequencyl donor variation for lymphocyta
cultures etc . One parameter that is not often taken into account is that astablishei
cell lines e .g . Chinese hamster V79, CH0 etc contain comprehensively re-arrangul
karyotypes involving deletions, additions, inversions, translocations etc. It
appears that many of these changes occurred at the time these cells became
established, but it is clear that sublinea are progressively changing and diverging .
In cells with such rearrangements genes concerned with DNA repair, cell division
regulation, chromosome stability etc may well function abnormally due to 'position
effects' or gene dosage effects, as for the activation of oncogenes . Such changes
may influence the response of a particular subline to clastogens . There is a paucity
of comparative tests on clastogens in different cell lines, or sublines . However
discordant results have been obtained both due to differences in protocol and to
inherent differences in the cells themselves . Primary cells e .g . human lymphocytes
do not have the problem of tearranged and diverging karyotype . However, these cell
are terminally differentiated and have to be induced to divide in culture, also donor
variation can result in at least quantitative variations in response . However, ou
oalance, the case for using primary lines appears to be stronger than the case fo•
established lines . This poster will review the karyotypic changes that have occurred
in the CHO and V79 sublines since their isolation and the results of testing with the
same chemicals with both types of line .
594
USE Of INTERPHASE ANALYSYS TO DETECT CHEMICALLY INDUCED ANEUPLOIDY IN CULTURED CELLS .
Vagnarelli P . . De Sario A . . Raismndi E.. Scariolo S. and De Csrli L .
Dipartimento di Genetica e Microbiologia. Universita di Pavia . via S.Epitaaio 14 . Pavia . Italy.
Ia rilu hybridization with cnromosome-specda DNA probes has Wen exploited for developmq an is ritro assay for
chemically inducea aneuploidy . The following probes have been tested : T*7 which idenGfies a 100 fold repeated fraqment in
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