Vol 31, Part I - forums.sou.edu • Index page - Southern Oregon ...

ABSTRACTS – Symposia
both cell lines...In SiHa cells, drug treatment induced a significant
and rapid shutdown of cellular proliferation resulting
from a global arrest of the cell cycle...CaSki cells also exhibited
a significant decrease in cellular proliferation; however
the cell population arrested at the G 1
/S phase transition following
treatment with AAPF CMK
. In both cell lines, the HPV-
16 E7 oncoprotein and the targets, pRb and E2F1, showed
no significant difference after treatment...In CaSki cells, p53
and p21 protein levels are significantly increased at 24 hours
with a concomitant increase in p21 mRNA after AAPF CMK
treatment...Although no difference in p53 and p21 protein
levels was detected in SiHa cells after drug treatment, a significant
increase in p21 mRNA was observed.. .Therefore,
AAPF CMK
treatment may potentially disrupt the ability of
HPV-16 E6 to completely inhibit p53 activity...Despite the
progress made by screening and vaccines, HPV infection
remains a serious worldwide health problem that warrants
research into additional treatment options.
88 From Our Phones To Our Bones: Mechanisms of Cadmium-Induced
Osteotoxicity, SARA J HEGGLAND
(Department of Biology, The College of Idaho, Caldwell, ID
83605; sheggland@collegeofidaho.edu).
Cadmium is a toxic metal that leaches into the environment,
most notably through the improper disposal of
electronics. Bone is a target site for cadmium toxicity...In
humans, exposure to cadmium is linked to the development
of osteoporosis. Our laboratory uses an osteoblast cell line
model to study the direct effects of cadmium in bone-forming
osteoblasts and on the extracellular matrix (ECM) these
cells produce.. . Our research demonstrates cadmium exposure
activates the ERK signaling pathway leading to osteoblast
apoptosis...More recently, we expanded our osteoblast
studies to clarify the impact of cadmium on the ECM. Osteoblasts
secrete an ECM primarily comprised of a calciumphosphate
crystalline and a collagenous protein component.
Our preliminary studies demonstrate that cadmium can be
deposited in the ECM, which led us to hypothesize that cadmium
exposure alters the nature of the ECM produced by
osteoblasts. After inducing cells to mineralize, we assessed
cadmium incorporation in the ECM and subsequent changes
in calcium, phosphate, and collagen deposition. Using surface
plasmon resonance and column chromatography we
explored cadmium-collagen binding interactions. We found
cadmium can bind collagen and with different affinity compared
to calcium. We are currently studying whether cadmium
alters collagen fibrillogenesis, which is the spontaneous
formation of the fibrillar structure found in bone. Collectively,
our work demonstrates that osteoblasts and the ECM
they secrete are targets for cadmium toxicity, providing a
mechanisms for how cadmium exposure may contribute to
the pathogenesis of osteoporosis.
Research funded by NIH-INBRE P20RR016454 and P20 GM103408 and
NIH R15ES015866 grants.
89 Mechanism of Acrylonitrile Carcinogenesis in Rat Brain:
The Potential Involvement of Oxidative Stress, XINZHU
PU 1 *, ZEMIN WANG 2 , SHAOYU ZHOU 2 , LISA M
KAMENDULIS 2 , and JAMES E KLAUNIG 2 ( 1 Department
of Biological Sciences, Boise State University, 1910
University Dr., Boise, ID 83725; 2 Department of Environmental
Health, Indiana University, 1025 E. Seventh Street,
Bloomington, IN 4740; shinpu@boisestate.edu).
Acrylonitrile is a heavily used chemical in the manufacturing
of plastics, acrylic fibers, and synthetic rubber.
Chronic exposure to acrylonitrile caused dose-related
increases in brain astrocytoma in rats. The International
Agency for Research on Cancer has ranked acrylonitrile as
a probable human carcinogen. The mechanism of acrylonitrile
carcinogenicity is not fully understood. The available
data from both in vivo and in vitro genotoxicity tests, while
largely negative, are mixed and inconclusive. Acrylonitrile
is mainly metabolized via glutathione conjugation. Studies
have demonstrated that acrylonitrile could deplete glutathione
in the cell and thus may interrupt red-ox balance since
glutathione is a major small-molecule antioxidant. Increased
oxidative stress and oxidative damage have been linked with
the induction of neoplasia by several non genotoxic chemical
carcinogens. We hypothesized that acrylonitrile could
cause oxidant stress and damage, which may be involved
in mechanism of acrylonitrile carcinogenicity. The results
of our studies showed that acrylonitrile caused persistent
oxidative damage in nuclear and mitochondria DNA in rat
astrocytes in vitro. It also caused oxidative DNA damage in
the cortex of rat brain following in vivo exposure. In addition
to stimulation of oxidative DNA damage, our studies
also showed that acrylonitrile triggered the induction of the
pro-inflammatory cytokines TNFα, IL-1β and CCL2, and the
growth stimulatory cyclin D1 and cyclin D2 genes. In addition,
antioxidant co-treatment effectively attenuated the oxidative
stress induced by acrylonitrile. These results suggest
the induction of oxidative stress and oxidative damage may
be involved in the development of rat brain tumors induced
by acrylonitrile.
90 Modulation of Atrogin-1 and the Ubiquitin Proteasomal
System by Anthracyclines in Left Ventricular Tissue in Rats,
NICOLE FRANK 1,2 *, SUELA KUMBULLA 1 , ADITI
JAIN 1 , JAMES C.K. LAI 1,2 , RICHARD OLSON 1,2 ,
BARRY CUSACK 1,2,3 , and ALOK BHUSHAN 1,2 ( 1 Department
of Biomedical and Pharmaceutical Sciences, College
of Pharmacy and ISU Biomedical Institute, Idaho State University,
Pocatello, ID 83209, USA; 2 Mountain States Tumor
and Medical Research Institute, Boise, ID 83712, USA;
1
Research Service, Dept. Veterans Affairs Medical Center,
Boise ID 83702; frannic2@pharmacy.isu.edu).
Anthracyclines are widely used to treat cancers, but
may also cause a cumulative dose-related cardiotoxicity.
One possible mechanism of cardiotoxicity relates to effects
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