Nitrosamine formation from amines applied to the skin of mice after and before exposure to nitrogen dioxide.
Skin lipids of mice exposed to NO2 contain lipid-soluble nitrosating agent(s) (NSA) that react in vitro with amines to produce nitrosamines. To test whether this reaction occurs in skin, we exposed mice to 50 ppm NO2 for 4 h and, 20 h later, applied 25 mg morpholine or N-methylaniline to the skin, which was then analyzed for the corresponding nitrosamine. When morpholine was applied, mean N-nitrosomorpholine yield was only 0.3 nmol/mouse (not significant). When N-methylaniline was applied and mice were killed after 10-40 min, N-nitroso-N-methylaniline yield in the skin was 13-21 nmol/mouse of which 87% occurred in the hair. NSA formation when mice were exposed to 6.5 ppm NO2 was only 0.15% of that for exposure to 50 ppm NO2. NSA occurred mostly in surface lipids of the skin and its in vitro reaction to give nitrosamines was not inhibited by alpha-tocopherol. When morpholine was painted and mice were then exposed to 55 ppm NO2 for 30 min, the skins contained 19 nmol N-nitrosomorpholine/mouse, attributed to a direct reaction between NO2 and the amine. We concluded that nitrosamine formation in skin by this direct reaction may be more important than the reaction of amines with NO2-derived NSA.
Mirvish
S S
SS
Eppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha 68105.
Ramm
M D
MD
Sams
J P
JP
Babcook
D M
DM
D000814:Aniline Compounds / Q000378:metabolism; D000818:Animals; D008297:Male; D051379:Mice; D009025:Morpholines / Q000378:metabolism; D009585:Nitrogen Dioxide / Q000378:metabolism*; D009602:Nitrosamines / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*
D000814:Aniline Compounds; D009025:Morpholines; D009602:Nitrosamines; C002741:N-nitrosomorpholine; C037574:morpholine; C014102:N-methyl-N-nitrosoaniline; D009585:Nitrogen Dioxide; C021313:methylaniline