Mutagenicity, DNA damage and DNA adduct formation by N-nitroso-2-hydroxyalkylamine and corresponding aldehydes.
The potent carcinogen N-nitrosodiethanolamine (NDELA) becomes mutagenic to Salmonella typhimurium TA98 and TA100 when activated by alcohol dehydrogenase from yeast or horse liver. Metabolic pathways different from alpha-oxidation might therefore be important for the activation of N-nitroso-2-hydroxyalkylamines such as NDELA. In an in-vitro test system (Namalva cells), neither NDELA nor N-nitrosoethyl-2-hydroxyethylamine was genotoxic, whereas the corresponding metabolites from alcohol dehydrogenase-mediated oxidation, N-nitroso-2-hydroxymorpholine and N-nitrosoethylethanalamine, induced single-strand breaks even at low doses. An immuno-slot-blot assay was used to study the formation of O6-2-hydroxyethyldeoxyguanosine in rat liver after oral administration of different N-nitroso-2-hydroxyalkylamines. When given at equimolar doses (0.375 mmol/kg), DNA hydroxyethylation was considerably lower (6.7 mumol/mol deoxyguanosine) with NDELA than with N-nitrosoethyl-2-hydroxyethylamine (48.7 mumol/mol deoxyguanosine) or N-nitrosomethyl-2-hydroxyethylamine (72.1 mumol/mol deoxyguanosine). N-Nitroso-2-hydroxymorpholine did not form detectable levels of O6-2-hydroxyethyldeoxyguanosine.
Scherer
G
G
Department of Food Chemistry, University of Kaiserslautern, Germany.
Ludeke
B
B
Kleihues
P
P
Loeppky
R N
RN
Eisenbrand
G
G
D000447:Aldehydes; D000818:Animals; D002273:Carcinogens; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D004052:Diethylnitrosamine / Q000378:metabolism / Q000633:toxicity* / Q000031:analogs & derivatives; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens; D051381:Rats; D011919:Rats, Inbred Strains
D000447:Aldehydes; D002273:Carcinogens; D009153:Mutagens; C014129:N-nitrosodiethanolamine; D004052:Diethylnitrosamine; D004247:DNA