Potential mechanisms of tumorigenic action of diethanolamine in mice.
Diethanolamine (DEA), a secondary amine found in a number of consumer products, reportedly induces liver tumors in mice. In an attempt to define the tumorigenic mechanism of DEA, N-nitrosodiethanolamine (NDELA) formation in vivo and development of choline deficiency were examined in mice. DEA was administered with or without supplemental sodium nitrite to B6C3F1 mice via dermal application (with or without access to the application site) or via oral gavage for 2 weeks. Blood levels of DEA reflected the dosing method used; oral greater than dermal with access greater than dermal without access. No NDELA was observed in the urine, blood or gastric contents of any group of treated mice. Choline, phosphocholine and glycerophosphocholine were decreased </=62-84% in an inverse relation to blood DEA levels. These data demonstrated a lack of NDELA formation in vivo at tumorigenic dosages of DEA but revealed a pronounced depletion of choline-containing compounds in mice. It is suggested that the latter effect may underlie DEA tumorigenesis in the mouse.
Stott
W T
WT
Toxicology and Environmental Research and Consulting, Dow Chemical Company, Bldg. 1803, Midland, MI 48674, USA. wstott@dow.com
Bartels
M J
MJ
Brzak
K A
KA
Mar
M
M
Markham
D A
DA
Thornton
C M
CM
Zeisel
S H
SH
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002273:Carcinogens / Q000378:metabolism*; D002794:Choline / Q000378:metabolism; D002796:Choline Deficiency / Q000139:chemically induced*; D004052:Diethylnitrosamine / Q000031:analogs & derivatives* / Q000378:metabolism; D004983:Ethanolamines / Q000008:administration & dosage* / Q000097:blood / Q000633:toxicity; D005766:Gastrointestinal Contents / Q000737:chemistry; D005997:Glycerylphosphorylcholine / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000187:drug effects; D008297:Male; D051379:Mice; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010767:Phosphorylcholine / Q000378:metabolism; D012977:Sodium Nitrite / Q000008:administration & dosage; D013109:Sphingomyelins / Q000378:metabolism
D002273:Carcinogens; D004983:Ethanolamines; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D013109:Sphingomyelins; D010767:Phosphorylcholine; C014129:N-nitrosodiethanolamine; D004052:Diethylnitrosamine; D005997:Glycerylphosphorylcholine; C020283:diethanolamine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D012977:Sodium Nitrite; D002794:Choline