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Carcinogenic tobacco-specific nitrosamines induction of apurinic/apyrimidinic sites in DNA of human oral cells

Award Number: R03CA259652
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/05/2023
PERIOD OF PERFORMANCE END DATE: 12/31/2025

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Carcinogenic tobacco-specific nitrosamines induction of apurinic/apyrimidinic sites in DNA of human oral cells - Project Summary Cigarette smoking is the leading cause of lung and oral cancer in the United States. Smokeless tobacco causes cancer of the mouth, esophagus and pancreas. The health effects of e-cigarettes are still under investigation but may disturb oral cavity homeostasis and cause lung and cardiovascular diseases. The tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) are classified as human carcinogens by the International Agency for Research on Cancer, and are recognized causes of these diseases. Metabolic activation of NNK and NNN results in formation of reactive electrophiles that modify DNA to produce a variety of products such as N7-[4-(3-pyridyl)-4-oxobut-1-yl]-deoxyguanosine (N7POBdG) that can result in apurinic/apyrimidinic (AP) sites in DNA by facile hydrolysis of the base- deoxyribonucleoside bond; other tobacco constituents may also induce AP sites. AP site accumulation may initiate the carcinogenic process. Oral cells provide the direct link between tobacco use and oral cancer in humans and elevated DNA damage has been found in oral cells of tobacco users. We propose to analyze AP sites in oral cell DNA with two specific aims: to develop a highly sensitive mass spectrometric method to quantify AP sites in human oral cell DNA, and to quantify AP sites in oral cell DNA induced by cigarette smoke, smokeless tobacco and e-cigarettes. The goals are to establish oral cell DNA AP sites as biomarkers of tobacco induced DNA damage in cigarette smokers, smokeless tobacco users, and e-cigarette users, and to ultimately identify susceptible tobacco users and design effective strategies to prevent cancer. This study may also provide preliminary data for a large epidemiologic study. We have strong preliminary data to support this proposal.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2023	MICHIGAN TECHNOLOGICAL UNIVERSITY	1400 TOWNSEND DR	HOUGHTON	MI	49931	HOUGHTON	USA	Cancer Cause and Prevention Research	000	3	4/29/2026	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2023	MICHIGAN TECHNOLOGICAL UNIVERSITY	1400 TOWNSEND DR	HOUGHTON	MI	49931	HOUGHTON	USA	Cancer Cause and Prevention Research	000	3	12/4/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2025	2023	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Cancer Cause and Prevention Research	001	2	1/16/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $77,500 )
2023	2023	MICHIGAN TECHNOLOGICAL UNIVERSITY	1400 TOWNSEND DR	HOUGHTON	MI	49931	HOUGHTON	USA	Cancer Cause and Prevention Research	002	3	9/11/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$71,741
2023	2023	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Cancer Cause and Prevention Research	001	2	9/11/2023	NON-COMPETING CONTINUATION	-$71,741
2023	2023	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Cancer Cause and Prevention Research	000	2	12/9/2022	NON-COMPETING CONTINUATION	$77,500
														Subtotal = $77,500

Issue Date FY: 2022 ( Subtotal = $77,500 )
2022	2022	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Cancer Cause and Prevention Research	000	1	1/31/2022	NEW	$77,500
														Subtotal = $77,500

Grand Total All Awards = $155,000

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Carcinogenic tobacco-specific nitrosamines induction of apurinic/apyrimidinic sites in DNA of human oral cells

Award Number: R03CA259652

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 06/05/2023

PERIOD OF PERFORMANCE END DATE: 12/31/2025

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