N-nitrosamino phosphates are unlikely transport forms for activated nitrosamines

J Cancer Res Clin Oncol. 1990;116(6):569-74. doi: 10.1007/BF01637076.

Abstract

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.

MeSH terms

  • Animals
  • Biological Transport
  • Biotransformation
  • Dimethylnitrosamine / analogs & derivatives
  • Dimethylnitrosamine / metabolism
  • Liver / metabolism
  • Male
  • Nitrosamines / metabolism*
  • Nitrosamines / pharmacokinetics*
  • Organophosphates / metabolism*
  • Rats
  • Rats, Inbred Strains

Substances

  • Nitrosamines
  • Organophosphates
  • 1-(N-ethyl-N-nitrosamino)ethyl phosphate
  • nitrosobenzylmethylamine
  • Dimethylnitrosamine