Inhibition of repairable DNA-damage in Escherichia coli K-12 cells recovered from various organs of nitrosamine-treated mice by vitamin A, phenethylisothiocyanate, oleic acid and triolein.
The influence of various dietary constituents--phenethylisothiocyanate (PEITC), oleic acid (OA), triolein (TO), and vitamin A (ROL)--on the genotoxic activity of nitrosamines (NDMA, NDELA, NPYR) was investigated. For this purpose differential DNA repair assays with Escherichia coli K-12 strains were performed in vitro and in vivo with mice. Under in vitro conditions (liquid holding), all compounds reduced nitrosamine induced DNA-damage in the indicator bacteria in the dose range 1-10 micrograms/ml, the ranking order of efficiency being PEITC greater than OA greater than ROL greater than or equal to TO. In animal-mediated assays, acute oral treatment with PEITC (17-150 mg/kg), 2 h before nitrosamine administration, resulted in a marked decrease of nitrosamine genotoxicity in liver, kidneys, lungs and in the blood. Also in other organs (spleen, testes) an increase in differential survival (which serves as a measure for repairable DNA damage) occurred. With ROL only a comparatively moderate antigenotoxic effect was obtained at a high dose level (250 mg/kg) under identical experimental conditions. OA (2000 mg/kg) and TO (16,000 mg/kg) were completely inactive. Upon repeated treatment (consecutive oral administration of the putative antigenotoxins over 4 days, a final treatment 24 h before nitrosamine administration) PEITC (150 mg/kg/day), ROL (80 mg/kg/day) and OA (2000 mg/kg/day) had no influence on the genotoxic effects of the nitrosamines. Repeated treatment with TO (4000-16,000 mg/kg/day) resulted in a moderate dose-dependent reduction of NDMA-induced DNA-damage in the indicator bacteria, whereas in combination with NPYR only a marginal effect was observed. Biochemical experiments indicated that the antigenotoxic effects of PEITC seen under in vivo conditions were due to inhibition of alpha-hydroxylation of the nitrosamines, whereas ROL and TO appeared not to interfere strongly with this metabolic activation step. Our results indicate that in vitro assays do only partly reflect the antigenotoxic properties of the different food constituents in vivo and that animal-mediated DNA repair assays with E. coli strains are an appropriate approach to study the effects of modifiers of nitrosamine genotoxicity in the living animal.
Knasmüller
S
S
Institut für Tumorbiologie und Krebsforschung, Universität Wien, Austria.
Huber
W W
WW
Kienzl
H
H
Schulte-Hermann
R
R
D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D004249:DNA Damage; D004260:DNA Repair; D004269:DNA, Bacterial / Q000187:drug effects; D004032:Diet; D004926:Escherichia coli / Q000235:genetics*; D017879:Isothiocyanates; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008168:Lung / Q000187:drug effects; D008297:Male; D051379:Mice; D009602:Nitrosamines / Q000037:antagonists & inhibitors / Q000633:toxicity*; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology; D013154:Spleen / Q000187:drug effects; D013737:Testis / Q000187:drug effects; D013861:Thiocyanates / Q000494:pharmacology; D014304:Triolein / Q000494:pharmacology; D014801:Vitamin A / Q000494:pharmacology
D016587:Antimutagenic Agents; D004269:DNA, Bacterial; D017879:Isothiocyanates; D009602:Nitrosamines; D009829:Oleic Acids; D013861:Thiocyanates; D014801:Vitamin A; D014304:Triolein; D019301:Oleic Acid; C058305:phenethyl isothiocyanate