Project: Research project


Several intermediate biomarkers have been linked to specific steps of human
carcinogenesis, and these biomarkers have been associated with risk for
cancer. This proposed study will focus on intermediate biomarkers
measuring drug and procarcinogen metabolism (cytochrome P450 and
glutathione S-transferase), binding of agents to DNA and DNA repair (DNA
Binding, UDS and ADPRT) and cell proliferation (ODC and [(3)H]thymidine
incorporation). The primary aim of this study is to develop and to compare
the experimental testing of these biomarkers of cancer susceptibility in
human mononuclear leukocytes and in the epithelium giving rise to breast
and colorectal cancer ("target tissue"). The working hypothesis is that
the measurements of these biomarkers in human mononuclear leukocytes may
partially reflect the biological responses in target tissues. The
correlation between measurements in leukocytes and target tissues will be
investigated. The secondary aim is to explore the possible application of
these intermediate biomarkers in measuring the biological responses to
chemopreventive agents. The correlation between changes in leukocytes and
the target tissue will be analyzed as well as the beneficial effects of
different agents. Furthermore, the correlation between changes in
different markers will also be evaluated. This analysis will provide
evidence demonstrating that certain markers are regulated similarly by the
same agent. Two groups of potential chemopreventive agents that will be
tested in exploratory human trials initially include antiestrogen
(tamoxifen) and antioxidants (vitamin C and beta-carotene). The Institutional Plan: CPRI has ongoing funded case-control, cohort, and
intervention research; the ultimate aim of all of CPRI's research is to
lower risk for cancer in humans. This research leads directly into Dr.
Hu's proposal. CPRI has had and will continue to have persons paid to
advise and support Dr. Hu in laboratory and field disciplines. The proposed study meets the award's criteria of "...development and
experimental testing of hypothesis about cancer prevention and control in
people, through the stage of confirming results using defined populations,
to the development and demonstration of cancer control technology". The
outcome of the human studies will validate the potential usefulness of
these biochemical measurements in human leukocytes as markers to predict
the beneficial effect of a given agent in future cancer intervention trials
developed by our Institute.
Effective start/end date8/1/927/31/97


  • National Institutes of Health
  • National Institutes of Health: $82,355.00
  • National Institutes of Health: $65,172.00
  • National Institutes of Health: $88,560.00
  • National Institutes of Health
  • National Institutes of Health


Mononuclear Leukocytes
ADP Ribose Transferases
Estrogen Receptor Modulators
beta Carotene
Tumor Biomarkers
DNA Repair
Cytochrome P-450 Enzyme System
Ascorbic Acid
Colorectal Neoplasms
Cell Proliferation


  • Medicine(all)