The Toxicologist - Society of Toxicology

DNA in the kidney medulla, grandular stomach and small intestine did not significantly
increased up to 200 mg/kg/day group. No cytotoxic observation was found
in any organ at 50 mg/kg/day group except slight centrilobular single cell necrosis
was found in the liver. These findings indicate that the Comet assay detected DNA
damage in the tumor target sites. In the kidney, these results suggest that DEN
exert genotoxic effects specifically in the kidney cortex.
322 OPTIMAL CONDITIONS FOR PERFORMANCE OF THE
COMET ASSAY USING A THREE-DIMENSIONAL
HUMAN EPIDERMAL MODE.
H. Kojima and M. Hojyo. Division of Pharmacology, National Institute of Health
Sciences, Tokyo, Japan.
To evaluate the risk of genotoxicity when human skin is exposed to chemicals, we
attempted to determine optimal conditions for the comet assay using a three-dimensional
human epidermal model (LabCyte EPI-MODEL: epidermal model,
Japan).
In this study, the well-characterized metabolically activated genotoxicants, cyclophosphamide
(CP), 2-aminoanthracene (2-AA), and nitrosodimethilamine
(NDA), were utilized for the comet assay using an epidermal model to evaluate
metabolic activation of chemicals.
The comets of 2-AA and NDA increased dose-dependently on the epidermal models
treated for 24 hours, while the results were ambiguous when treatment lasted for
four hours. CP, on the other hand, did not induce comets.
We consider the comet assay using an epidermal model to be potentially useful in
being able to detect indirect genotoxicants regardless of metabolic activation.
323 GENOTOXICITY OF STYRENE-ACRYLONITRILE
TRIMER IN WEANLING F344 RATS.
R. S. Chhabra1 , C. A. Hobbs2 , L. Recio2 , J. Winters2 , K. Shepard2 , P. Allen2 ,
M. Prajapati2 , M. Streicker3 and K. L. Witt1 . 1National Toxicology Program,
NIEHS, Research Triangle Park, NC, 2Genetic and Molecular Toxicology, ILS, Inc.,
Research Triangle Park, NC and 3Investigative Toxicology, ILS, Inc., Research Triangle
Park, NC.
Styrene-acrylonitrile trimer (SAN trimer) is a byproduct in production of acrylonitrile
styrene plastics. The chemical was identified at a Superfund site in Dover
Township, NJ and was tested by the National Toxicology Program (NTP) in a 2-yr
perinatal dosed-feed study in rats. It was also tested by the NTP in an Ames assay
and was negative. To further characterize the toxicity of SAN trimer, the NTP evaluated
its genotoxicity in a combined micronucleus (MN)/Comet assay in 4-wk old
male and female F344 rats. SAN trimer was administered by gavage (37.5, 75, 150,
or 300 mg/kg) once daily for 4 days. The lower doses approximated those used in
the NTP 2-year feeding study. Samples were collected 4 hr after final dosing for
measurement of micronucleated reticulocyte (MN-RET) frequencies in blood by
flow cytometry and DNA damage in blood, liver, and brain (cerebrum and cerebellum)
using the Comet assay. A dose-related increase (p < 0.0001) in MN-RET was
seen in both male and female rats administered SAN trimer; significant increases in
MN-RET were seen in the 300 mg/kg males and the 150 and 300 mg/kg females.
The RET population was reduced in the high dose male rats, suggesting chemicalrelated
bone marrow toxicity. Dose-related increases in DNA damage, measured as
% tail DNA in the Comet assay, were seen in the brains of both male (p < 0.0074)
and female (p < 0.0001) rats; significantly increased damage was seen in the 300
mg/kg males and the 150 and 300 mg/kg females compared to controls. Increased
levels of DNA damage were also seen in liver cells and leukocytes of male and female
rats treated with SAN trimer. No indication of chemical-related cytotoxicity
was seen in any of the tissues examined for DNA damage. In summary, the results
of this subacute MN/Comet assay indicate induction of significant genetic damage
in multiple tissues of weanling F344 male and female rats after oral exposure to
SAN trimer.
324 THE EVALUATION OF MN AND SCE FREQUENCIES
AND OXIDATIVE STRESS STATUS OF HOSPITAL STAFF
OCCUPATIONALLY EXPOSED TO LOW DOSES OF
IONIZING RADIATION. DOES THE LOW DOSE
STIMULATE DEFENSE STATUS?
A. Aydin 1 , A. Eken 2 , O. Erdem 2 , C. Akay 2 , B. Soykut 2 , A. Sayal 2 and I.
Somuncu 3 . 1 Toxicology, Yeditepe University, Faculty of Pharmacy, Istanbul, Turkey,
2 Toxicology, Gulhane Military Medical Academy, Ankara, Turkey and 3 Radiology,
Gulhane Military Medical Academy, Ankara, Turkey. Sponsor: A. Karakaya.
Ionizing radiation is known to induce oxidative stress through generation of reactive
oxygen species (ROS) resulting in imbalance of the pro-oxidant and antioxidant
activities and cellular DNA damage. The aim of this study was to evaluate the
oxidative stress status and the genotoxic effects in radiology unit staff. Antioxidant
enzyme activities and malondialdehyde (MDA) levels were measured. The micronucleus
(MN) and sister chromatid exchanges (SCE) techniques were used. This
study included 40 exposed individuals together with 30 control subjects. The activities
of erythrocyte CuZn-SOD activities and erythrocyte Se-GPx activities observed
for the exposed groups were statistically very significantly higher than in the
control group (p