Retroviral vectors have been used to transfer and express cyclooxygenase (COX) 1and 2. 10T1/2 and AS52 cells that stably express high levels of retroviral vector transferred murine COX-1 or -2 were developed and characterized. The expressed COX-2 preferentially utilized specific endogenous AA (arachidonic acid) pools (i.e., TPA released but not Ca ionophore released AA). Furthermore, NO (nitric oxide) was shown to enhance both COX-1 and -2 activities. The TPA and NO findings may be relevant to the COX's hypothesized role in carcinogenesis and inflammation. Additionally, we showed that COX-1 and -2 metabolically activated 1,1-dimethylhydrazine, aflatoxin B1, and N-acetylbenzidine to mutagens. Furthermore, the cells were useful in identifying NSAIDs which were selective for COX-1 and COX-2.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES021121-07
Application #
5202108
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
1995
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code