Oxidation of unsymmetrically deuterated N-nitrosodimethylamine by acetone-induced rat liver microsomes was found to proceed with little or no regioselectivity with respect to enzymatic attack on the syn versus anti methyl groups, in contrast to the high stereospecificity expected from the action of most enzymes. Acetylation of the potent bacterial mutagen, fecapentaene-12, was shown to improve its solubility in dimethylsulfoxide, allowing the compound to be tested in higher molar doses than in previous carcinogenicity studies with the underivatized material; despite very high exposures on repeated skin painting of this material in SENCAR mice, no increase in tumor incidence was observed. This was true whether or not Vitamin E was added to the test agent to prevent atmospheric oxidation during application. The results are inconsistent with the conclusion that the potently mutagenic fecapentaenes are mammalian carcinogens.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CP004542-19
Application #
3853397
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
19
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Division of Cancer Epidemiology and Genetics
Department
Type
DUNS #
City
State
Country
United States
Zip Code