Environmental and Molecular Mutagenesis - Legacy Tobacco ...

ackground peak respons ) . SCA frequency was increased by four quinolones, PD 117579
(10 ug/ml minimal clasto enic concentration, 4 .5-fold background peak response) . PD
117962 (45 ug/ml minimaclastogenic concentration, 9 .3-fold background peak response),
ciprofloxacin (400 ug/ml minimal clastogenic concentration, 8 .9-fold background peak
response), and ofloxacin (1800 ug/ml minimal clastogenic concentration, 6 .3-fold
background peak response) . Norfloxacin and nalidixic acid were negative for all three
endpoints . Thus, the SCA test is the moat sensitive of the three endpoints assessed .
However, literature reports indicate that the two quinolones that increased SCA
frequency in vitro only at high concentrations (ciprofloxacin, ofloxacin) failed to
exhibit clastogenic activ-ity-in animals yr man, indicating that these high
concentration in vitro effects may be of limited biological significance . Thus, an in
vitro assessment of the clastogenic activity of quinolones should be coupled with an in
vivo test to assess the biological significance of any in vitro activity .
577
Measurement of Mutational Spectra in Human Tissues
William G . Thilly, Phouthone Keohavong, Neal Cariello, John Hanekamp
Center for Environmental Health Sciences
MIT E18-666 Cambridge, MA 02139
Application of mutational spectra to diagnose the causes of genetic change in humans
will be discussed . Recent advances in technology, including PCR improvements,
designed to obtain such spectra from human cells and tissues will be reviewed .
Topics to be covered are signal/noise requirements, multi-copy sequences and means
to obtain spontaneous spectra from individuals .
Sponsored by U .S . Department of Energy Office of Health and Environmental Research
and the U .S . National Institute of Environmental Health Sciences. •
578
LACK OE' CYTOGENETLC EFE'E:CTS IN BONE MARROW OF TWO STRAINS OF MICE CHRONICALLY EXPOSfSD
TO CLGARETTE SMOKE . M .A . Thomas*, D . Gulati**, J .P . Wojciechowski**, P . Sabharwal**,
and C .G . Gairola* . *Graduate Center for Toxicology, and Tobacco and Health Research
Institute, University of Kentucky, and **Rnvironmental Health Research and Testing,
Inc ., Lexington, KY .
This study was conducted to determine if chronic exposure to cigarette smoke induces
cytogenetic damage in the bone marrow of aryl hydrocarbon hydroxylase- (AHH) inducible
(C57BL/6J) and non-inducible (DBA) strains of mice . Using a nose only exposure system
groups of female mice were chronically exposed (50 - 70 weeks) twice daily to mainstream
(ttS) or sidestream (SS) cigarette smoke, from high-tar/high-nieotine University
of Kentucky Reference cigarettes (2R1) . Room (RC) and sham control (SH) groups were
also examined . Pulmonary AHH activity was increased 2-3 fold in C57BL but not DBA
mice . Blood carboxyhemoglobin (%COHb) levels were increased approximately 11 and 22
fold for MS and SS groups, respectively, in both strains . Average intake values for
smoke total particulate matter were 17 .1 and 6 .9 mg/kg per exposure-session, for MSand
SS- exposed groups, respectively . These dats confirmed effective inhalation of
smoke by exposed animals . Two cytogenetlc endpoints, sister-chromatid exchange (8Cg)
and micronucleus (MN) formation, were examined in isolated bone marrow cells . tlnder
these exposure conditions neither MS nor SS cigarette smoke induced an increase in
frequency of SCE or MN in either strain of mice . (Supported by KTRB 41031) .
579
GENETIC ANALYSIS OF HUMAN DNA REPAIR GENES, L. H . Thompson, C . A . Weber,
K .W. Brookman, N .J . Jones, E .P . Salazar, and M .J. Sicilianot, Biomedical Sciences Division, Lawrence
Livermore National Laboratory, P.O. Box 5507, Livermore, CA 94550 and tDepartment of Molecular
Genetics, University of Texas System Cancer Center, Houston TX 77030
Human genes that control DNA repair were identified by complementing repau-deficient hamster mutant
lines with human chromasomes in hybrid cells or by transfecting with human DNA . Nucleodde excision
repair (NER) genes, which control UV radiation sensidviry, are located on human chromasomes 2,13,16,
and 19 . A total of eight complementadon groups of NER genes are now identified among rodent mutants .
The human ERCC2 (Excision Repair Crass Complementing) gene, which corrects CHO mutant WS and
was previously cloned in cosmids, was used to isolate homologous cDNA ciones from Okayama's pcD2
expression library. Nucleotide sequencing of an incomplete cDNA clone and ERCC2 S' genomic
sequences identified an open reading frame . The protein coding region of ERCC2 has a atrildng 5296 a a .
identity with the RAD3 gene in yeast This similanty suggests conservadon of function and the possibiliry
http://legacy.library.ucsf.edu/tid/clb93d00/pdf
A
1989 EMS Abstracts 199
Notes