N-Nitrosodiethylamine mutagenicity at low concentrations

Toxicol Lett. 2003 Nov 1;145(1):36-45. doi: 10.1016/s0378-4274(03)00263-7.

Abstract

N-Nitrosodiethylamine (NDEA) requires metabolic activation by cytochrome P450 enzymes, leading to electrophile species that react in DNA. Although, carcinogenicity is not an end point in genotoxicity assays, NDEA has been considered a weak carcinogen. In this study, we carried out an analysis of the mutagenicity at low concentrations of NDEA. Using SOS chromotest in the presence of metabolic activation, we detected positive mutagenicity response for NDEA doses between 0.75 and 36.46 microg/ml. In Ames test, using more sensitive strains in the presence of S9 metabolic activation mixture (S9 mix), positive results were also detected for NDEA doses between 1.01 x 10(-3) and 50.64 x 10(-3 microg per plate. Our results indicate that NDEA mutagenicity can be detected at low concentrations when more sensitive conditions are used.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylating Agents / toxicity*
  • Animals
  • Diethylnitrosamine / toxicity*
  • Dose-Response Relationship, Drug
  • Escherichia coli / drug effects
  • Escherichia coli / genetics
  • Genotype
  • Histidine / genetics
  • In Vitro Techniques
  • Microsomes, Liver / metabolism
  • Mutagenicity Tests
  • Mutagens / toxicity*
  • Rats
  • Rats, Sprague-Dawley
  • Salmonella typhimurium / drug effects
  • Salmonella typhimurium / genetics
  • Survival Analysis

Substances

  • Alkylating Agents
  • Mutagens
  • Diethylnitrosamine
  • Histidine