New analytical methodology is to be developed to measure DNA adducts arising from occupational human exposure to ethylene, ethylene oxide, butadiene, styrene and propene. These chemicals were selected since they are widely used and genotoxic. Also they are anticipated to give the same types of DNA adducts. The proposed methodology basically comprises four steps: (1) isolate the DNA from a biological sample; (2) separate the DNA adducts from the bulk of the DNA; (3) electrophore derivatize the adducts; and (4) detect the electrophoric products by gas chromatography - electron capture negative ion-mass spectrometry (GC-ECNI-MS). Electrophoric derivatization/GC-ECNI-MS has been selected because of the need for sensitive, definitive measurements. Current methodology is limited in these respects, which makes it difficult to make accurate assessments of exposure and risk. It is important to measure DNA adducts in human samples. DNA is an ultimate target in the body for carcinogenic and mutagenic chemicals. Measurements of DNA adducts can help to sort out uncertainties arising from exposure of individuals to multiple chemicals, and from individual variations in metabolism and lifestyle. Our understanding of the biological significance of chemical damage to DNA is dependent on our ability to measure it.

Agency
National Institute of Health (NIH)
Institute
National Institute for Occupational Safety and Health (NIOSH)
Type
Research Project (R01)
Project #
3R01OH002792-03S1
Application #
2277602
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1991-01-01
Project End
1994-12-31
Budget Start
1993-01-01
Budget End
1994-12-31
Support Year
3
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Northeastern University
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
039318308
City
Boston
State
MA
Country
United States
Zip Code
02115