Department of Health and Human Services Public Health Service, Grant Application

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Principal Investigator/Program Director (Last, first, middle):

Duesberg, Peter H

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DESCRIPTION: State the application's broad, iong-term objectives and specific aims, making reference to the health relatedness o the proec.esnb
concisely the research design and methods for achieving these goals. Avoid summaries of past accomplishments and the use of the first person. This abstract is
meant to serve as a succinct and accurate description of the proposed work when separated from the application. DO NOT EXCEED THE SPACE PROVIDED.

The long-term consumption of nitrite inhalants has been suggested since 1981 as a possible
contributing factor to AIDS. Epidemiological correlations have established a dose-response
relationship between nitrite consumption and AIDS risk, and the restriction in their use to the active
homosexual community correlates well with the restriction of Kaposi's sarcoma to homosexuals
with AIDS. Long-term exposure of mice to nitrites can result in immune suppression. However,
such toxicological experiments have thus far remained inconclusive, because they have not been
carried out at an adequate dose and length of time.
Following and extending unfinished studies by others from the mid-1980s, it is proposed here to
determine the effects of the long-term inhalation of nitrites on mice (e.g. 6 hrs per day, 5 days per
week, for 6.to 24 months). To distinguish between the roles of nitrites as autonomous pathogens
and as co-factors of HIV, murine retrovirus-infected and un-infected mice will be studied in
parallel. The parameters to be monitored include a) weight loss, b) anemia and lymphocytopenia,
c) clinical manifestations of immunodeficiency, particularly Pneumocystis pneumonia, d) evidence
for Kaposi's sarcoma. In addition we propose to study the effects of nitrites on the growth rate of
human T-cell lines in culture. Finally we plan to examine the Kaposi sarcomagenic potential of
nitrites on rodent cells in culture. Avoiding the toxicity to vital organs, like the lung and the bone
marrow, the cell culture system will permit us to test nitrites at higher-than-in-vivo concentrations.
This is critical to detect sarcomagenic potential, because Kaposi sarcomas are typically restricted to
humans with the highest cumulative lifetime doses of nitrites.
The proposed research would clarify whether immnuosuppression and/or Kaposi sarcoma can
result from long-term exposure to nitrite inhalants. Public health efforts aimed at AIDS prevention
might increase their effectiveness by discouraging the recreational use of nitrites and other
psychoactive drugs, thereby lowering the AIDS risk even of those already infected by HIV.

PERSONNEL ENGAGED ON PROJECT, INCLUDING CONSULTANTS/COLLABORATORS. Use continuation pages as needed to provide the required
information in the format shown below on all individuals participating in the project

Name
Position Title
Organization
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Name
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Peter H Duesberg
Professor
University of California at Berkeley
Otto G. Raabe
Professor-in-Residence
University of California, Davis
Mohammed A. Ai-Bayati
Assistant Research Toxicologist
University of California, Davis
Ruhong Li

Vstg Asst Prof Res Biochemist 1

l

University of California at Berkeley

Bryan Ellison
Graduate Student
University of California at Berkeley
S. Teague
Staff Research Associate IV
University of California, Davis
D. Uyeminami

Degree(s) Ph. D. Social Security No. 564-72-3481
Date of Birth (MM/DD/YY) 12/02/36 Role on Project Prin Investigator
Department Virus Laboratory
Degree(s) Ph.D. Social Security No. 525-90-7445
Date of Birth (MM/DD/YY) Role on Project Prin Invest (UCD)
Department Inst Toxicology Env Health
Degree(s) Ph.D. Social Security No.
Date of Birth (MM/DD/YY) Role on Project Vet. Pathologist
Department Inst Toxicology Env Health
Degree(s) Ph. D. Social Security No. 070-70-4704
Date of Birth (MM/DD/YY) 02/28/47 Role on Project Postdoc research
Department Virus Laboratory
Degree(s) Masters equivalent Social Security No. 567-77-0834
Date of Birth (MM/DD/YY) 08/30/67 Role on Project Predoc research
Department Virus Laboratory
Degree(s) Social Security No.
Date of Birth (MM/DD/YY) Role on Project Inhalation research
Department Inst Toxicology Env Health
Degree(s) Social Security No.
Date of Birth (MM/DDIYY) Role on Project Toxicolo ist
Department Inst Toxicology Env Health
Degree(s) Social Security No.
Date of Birth (MMIDD/YY) Role on Project Histopathologist
Department Inst Toxicology Env Health

Staff Research Associate II

University of California, Davis

M. Conard
Staff Research Associate I
University of California, Davis

PHS 398 (Rev. 9/91) Page 2 BB

PHS 398 (Rev. 9/91) Page 2
Number pages consecutively at the bottom throughout the application. Do Wg. use suffixes such as 3a, 3b.

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