N-nitrosamino phosphates are unlikely transport forms for activated nitrosamines.
Some of the target organs for nitrosamine carcinogenicity have a low activating capacity but many carcinogenic nitrosamines can be activated in the liver. Conjugates, such as phosphates, are chemically accessible reaction products of 1-OH-nitrosamines, and are either potential detoxication products or potential transport forms for activated nitrosamines. 14C-labeled 1-(N-ethyl-N-nitrosamino)ethyl phosphate was tested for its ability to enter primary rat hepatocytes but no uptake was detectable. No uptake was observable into fibroblasts and human leukocytes. N-Nitrosomethylbenzylamine is efficiently 1-C-hydroxylated by hepatocytes but the corresponding 1-C-phosphate was detectable neither in the cells nor in the surrounding medium. N-Nitrosamino-1-phosphates, unlike 1-glucuronides, therefore, do not seem to be important for nitrosamine toxicokinetics.
Frei
E
E
German Cancer Research Center, Institute for Toxicology and Chemotherapy, Heidelberg.
Frank
N
N
Wiessler
M
M
D000818:Animals; D001692:Biological Transport; D001711:Biotransformation; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D009602:Nitrosamines / Q000378:metabolism* / Q000493:pharmacokinetics*; D010755:Organophosphates / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D009602:Nitrosamines; D010755:Organophosphates; C060350:1-(N-ethyl-N-nitrosamino)ethyl phosphate; C014707:nitrosobenzylmethylamine; D004128:Dimethylnitrosamine