Environmental and Molecular Mutagenesis - Legacy Tobacco ...

1989 EMS Abstracts 217
reflux of glycine, glucose and creatinine, or in realistic frying of Notes
meat, competition with creatinine by L-tryptophan, L-proline, or both
has lowered the formation of IQs considerably . This approach provides
a feasible, practical means of inhibiting the production of IQs . The
metabolism of IQ in rats yields evidence of N-acetylation, N-demethylation,
hydroxylation on carbon 5 (excreted as O-glucuronide and 0sulfate)
and intestinal flora-mediated formation of 7-OH-IQ . Xanthineoxidase
reduction of 2-NO2-IQ yielded intermediates reacting with alfthymus
DNA, and giving 5 products, visualized upon hydrolysis by 3~Ppostlabeling
. Microsomal metabolism of IQ yielded the same 5 products,
CAd242i? anathOeAr~21~11fs~rNCampuntg`(supported in part of USPHS grants
630
DICHLOROMETHANE-INDUCED CYTOGENETIC DAMAGE IN HICE . B . Westbrook-Collinsl, J .W .
Allenl, A .D . Kligermanl, J .A . Campbell2, G .L . Erexson2, F . Kari3, and E . 2eiger3 .
1U .S . Environmental Protection Agency, RTP, NC 27711 USA ; 2Environmental Health
Research and Testing, Inc ., RTP, NC 27709 USA ; 3National Institute of Environmental
Health Sciences, RTP, NC 27709 USA .
Dichloromethane (DCM) or methylene chloride is a widely used industrial solvent
which causes lung and liver tumors in inhalation-exposed B6C3F1 mice (NTP, 1986) . In
the present studies, chromosome damage was studied in female 86C3F1 mice exposed to
DCN by subcutaneous or inhalation treatments . After a single subcutaneous injection
of either 2,500 or 5,000 mg/kg DCM, no increases in frequencies of sister chromatid
exchanges (SCEs) or chromosome aberrations (CAS) in bone marrow cells were observed .
Inhalation exposure to DCM for 10 days at doses of 4,000 or 8,000 ppm resulted in
significant increases in frequencies of SCEs in lung cells and peripheral blood
lymphocytes, CAs in lung and bone marrow cells, and micronuclei (MN) in peripheral
blood erythrocytes . The highest levels of increased damage ware observed for lung
cell CAs and blood erythrocyte MN (approximately two times control frequencies) and
bone marrow CAs (approximately four times control frequency) after 10 days .
Following a 3-month inhalation exposure to 2,000 ppm DCM, mice showed small but
significant increases in lung cell SCEs and peripheral blood erythrocyte MNr . It was
concluded that DCM is clastogenic following in vivo inhalation exposure . This
finding suggests that genotoxicity may play a role in the carcinogenic properties of
DCM in B6C3F1 female mice . (This is an abstract of a proposed presentation and does
not necessarily reflect U .S . EPA policy.) A
631
CHARACTERIZATION OF THE IN VITRO UNSCHEDULED DNA SYNTHESIS ASSAY USIYG PRIMARY LUNG
CELLS OF THE RAT . W-2 . Whong, J .D . Stewart, and T . OnB, Division of Respiratory
Disease Studies, National Institute for Occupational Safety and Health, Morgantown,
WV (USA)
Since genotoxic agents can be present in the environment as gases, vapors, and
airborne particles, inhalation becomes an important exposure route with the lung as a
major target for such genotoxicants . Therefore, primary lung cells, which retain
most of their original metabolic ability, may provide a useful cell system for evaluating
the pulmonary genotoxicity of chemicals with different genetic endpoints .
Previously, we had established the micronucleus and sister ehromitid exchange assays
in rat primary lung-cell cultures . In the present study, effort was made to incorporate
the in vitro unscheduled DNA synthesis (UDS) assay in the same cell culture
system . The autoradiograph method employed for detecting UDS was characterized, and
the assay was tested with a direct and an indirect-acting genotoxicants in both
alveolar macrophages and primary lung cells from rats . Data of a tisas oourse study
revealed that the optimal radioactive labeling was achieved after a 16-b incubation
with 3H-thymidine . Hydroxyurea at the concentration of 20 mlK effectively inhibited
the regular DNA synthesis . With this protocol, a dose-dependent UDS was induced by
Y-methyl-N'-nitroso-N-guanidine and 2-aminoanthracene in both rat alveolar sucrophages
and primary lung cells . These results indicate that primary rat lung cells in
culture possess DNA repair ability and that the UDS assay may be useful for assessing
the genotoxic effect of chemicals in this cell system .
632
:.h-LCCUS LItdI:E.') 'lI^7';'-M?C_-S IPT IN')UC_"OTT OF SCE 'nY °-1tT?C ;a ;w`MTE IN
f•:CUS : aaE 3^.^ .TE:. IN "IN VIVO" AS CC".?:'AYED TC "IN VI^_RO" T--S'S . S .M,
WLelgosz Pnd A .L.P?vlak, Inatitute of Hrnman GPnetics, ^olirh Ac^de^!y
of Sci,~nces, u_.7_9trzeszynskn 32, 60-479 ?ozn .!)A (Polend)
The e°fect of alleles of Ah lecur on the induction of SC- - as •tudied
in C57316 and in DBA2 mice +.•r.eeted t .a cs ' . :ith ben~o(^!pyr^nc (EY,
1C0 m,- -,Pr 1cg, p .o . ) . ='or mea-r.^em^nt^ of ch-n!;eo in fre-uency of SCE
http://legacy.library.ucsf.edu/tid/clb93d00/pdf