DNA-repair genes and vitamin E in the prevention of N-nitrosodiethylamine mutagenicity.
Nitrosamines are stable compounds, biologically and chemically inert unless activated. In biological systems, N-nitrosodiethylamine (NDEA) can be activated by a variety of enzymes, leading to aldehydes and/or intermediates which are themselves alkylating agents. Additionally, it has been shown that NDEA causes reactive oxygen species (ROS) production and induces mutagenicity. The cell defense seeks to neutralize ROS that escape the primary defense mechanisms (antioxidants) by DNA-repair mechanisms. NDEA is present at low concentrations in major dietary sources, like cured meats, salami, millet flour, and dried cuttlefish, where NDEA mutagenicity has been detected. These facts lead us to evaluate vitamin E as a ROS scavenger, in Escherichia coli mutants system, against genotoxicity induced by NDEA at low concentrations under exogenous metabolic activation. Statistical analysis were performed in order to compare the effects of NDEA-induced genotoxicity (a) between the mutants and the wild-type strains, at the same metabolic activation conditions and, (b) between the same strains in the presence or in the absence of vitamin E (150 muM). The indirect evaluation of ROS production by NDEA metabolizing shows that vitamin E protects E. coli cells proficient or deficient in the DNA-repair genes from cytotoxic effects. Our results underscore the role of scavenger molecules such as vitamin E in the diet, avoiding lesions induced by NDEA at low concentrations, via ROS, that could be repaired by nucleotide excision repair and base excision repair proteins.
Aiub
Claudia Alessandra Fortes
CA
Department of Biophysics and Biometry, Roberto Alcantara Gomes Biology Institute, Rio de Janeiro University State, Rio de Janeiro 20551-030, Brazil. aiub@hotmail.com
Pinto
Luis Felipe Ribeiro
LF
Felzenszwalb
Israel
I
D004260:DNA Repair / Q000235:genetics*; D004052:Diethylnitrosamine / Q000633:toxicity*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D016166:Free Radical Scavengers / Q000633:toxicity*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D017382:Reactive Oxygen Species / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology*
D016166:Free Radical Scavengers; D009153:Mutagens; D017382:Reactive Oxygen Species; D014810:Vitamin E; D004052:Diethylnitrosamine