The Toxicologist - Society of Toxicology

dicating widespread exposure. While health effects from phthalate exposure are not
understood, phthalates have endocrine disruption potential and have been implicated
as contributing to the obesity epidemic. Our study was conducted to reveal
the impact of in utero exposure to a phthalate on the biochemical profiles of brain
and reproductive organs from prepubertal pups born to dams administered butylbenzyl
phthalate (BBP). Pregnant rats were exposed by gavage daily during gestation
(gd 14-21) to vehicle or to BBP in vehicle at a level known to induce effects in
the offspring and at a level previously not shown to induce effects. Traditional phenotypic
anchors (e.g., anogenital distance, retained nipples) were measured in pups
(between pnd 0 and pnd 26). Tissues were collected from the dam on post natal day
(pnd) 21 (~3 wks after BBP administration), and from pnd 26 pups (~ 4 wks after
birth to dosed dams) and processed for metabolomics analysis. Student’s t-tests were
used to compare levels of metabolites among the BBP- and vehicle- exposed groups,
and multivariate analysis was used to determine metabolites that best separate
groups. Using t-tests, significant differences (control vs BBP groups) in levels of
metabolites in brain tissue (male and female) and testes were found for pups, but
not for dams. Principle component analysis and partial least squares projection to
latent structures discriminant analysis were applied to the metabolomics data and
revealed metabolites most important to the separation of all study groups. Overallthe
major metabolic perturbations were related to metabolic pathways which include
amino acids. This study demonstrates the use of metabolomics to reveal metabolic
perturbations in tissues of offspring following in utero exposure to chemicals.
2203 IN UTERO BAP-EXPOSURE LEADS TO
DYSREGULATION OF THE CARDIOVASCULAR
SYSTEM OF LEH RAT OFFSPRING IN LATE LIFE.
G. E. Jules 1 , M. M. Maguire 1 , A. Ramesh 2 and D. B. Hood 1 . 1 Neuroscience and
Pharmacology, Meharry Medical College, Nashville, TN and 2 Biochemistry and
Cancer Biology, Meharry Medical College, Nashville, TN.
Cardiovascular disease (CVD) affects over 71 million American adults and remains
the leading cause of death throughout Europe and the United States. Adult lifestyle
choices, nutritional habits, and levels of physical activity significantly contribute to
the development of CVD, which may be associated with intrauterine growth or
early events in childhood. An increasing body of evidence indicates that transplacental
exposure to PAHs at relatively high concentrations is linked to adverse birth
outcomes. Benzo[a]pyrene (BaP), a prototypical PAH, is known to cause a number
of effects, including atherogenic and cytotoxic effects in various species and tissues.
However the mechanisms of action by which prenatal BaP exposure results in adverse
effects on the development of fetuses and young children is not fully understood.
In this study, we proposed that prenatal exposure of Long Evans Hooded
(LEH) rat dams to BaP will result in deficits in cardiovascular development. Timepregnant
LEH rat dams were treated with 600ug/kg/BW of BaP for 4 days, starting
on gestation day 14. Offspring from both BaP-treated and control dams were then
sacrificed on post natal day (P) 0, 3, 5, 7, 9,11 and 53. Blood, heart and aorta were
harvested upon sacrifice and stored in liquid nitrogen. Microarray and quantitative
RT-PCR analysis of the heart and aorta was done to determine the effect of prenatal
BaP exposure on gene expression. In addition, western blot analysis was done to
determine the effect of BaP on the Sp transcription factors during the development
of the rat offspring. Microarray and qRT-PCR data show a number of genes to be
significantly altered, while there was a leftward shift in the developmental expression
of Sp3. These findings suggest that prenatal BaP exposure affects the normal
development of the cardiovascular system of LEH rat offspring.
2204 MODULATION OF OXIDATIVE DNA DAMAGE
BIOMARKER IN POSTMENOPAUSAL WOMEN BY
GREEN TEA POLYPHENOLS AND TAI CHI.
F. Wang 1 , L. Tang 1 , G. Qian 1 , S. Xue 1 , C. L. Shen 2 and J. Wang 1 .
1 Environmental Health Science, University of Georgia, Athens, GA and 2 Texas Tech
University Health Science Center, Lubbock, TX.
Osteoporosis is a degenerative bone disease characterized by low bone mass and
structural deterioration of bone tissue and postmenopausal women are high-risk
population. Etiological agents associated with osteoporosis include poor nutrition,
cytokines, hormones, and aging. Reactive oxygen species (ROS) are shown to be responsible
for the aging process and contribute to osteoporosis. Green tea polyphenols
(GTP) are capable of reducing the levels of ROS in human studies. On the
other side, Tai Cai (TC) exercise was shown to benefit osteoporosis by reducing
bone loss. However, the information on effects of GTP and TC, especially their
combined effects, on postmenopausal women is lacking. In this study, a total 160
postmenopausal women were recruited to participate in a 6-month placebo-controlled
randomized trial. Four treatment arms included placebo, GTP (500mg
daily), placebo+TC and GTP+TC. Blood and urine samples are collected at baseline,
1, 3 and 6 month after intervention for analysis of 8-hydroxyldeoxyguanosine
(8-OHdG) and GTPs by HPLC-Coularray. The average baseline levels of urinary
8-OHdG are comparable among 4 treatment arms (p=0.299). After 1-month intervention,
though no statistical significance among groups, the median level of 8-
OHdG decreased 43.9, 27.4, and 40.1% in GTP, TC, and GTP+TC groups, respectively.
After 3-month intervention, the median level of 8-OHdG further
decreased 62.4, 44.1, and 64.8% in GTP, TC, and GTP+TC groups, respectively
(p