Mutagenic activity of a nitrosated early Maillard product: DNA synthesis (DNA repair) induced in HeLa S3 carcinoma cells by nitrosated 1-(N-L-tryptophan)-1-deoxy-D-fructose.
HeLa S3 cells in suspension were incubated at 37 degrees C with various concentrations of the Amadori compound 1-(N-L-tryptophan)-1-deoxy-D-fructose (Trp-Fru), of its nitrosated analogue NO-Trp-Fru and of sodium nitrite, for varying periods of time, and were assayed for viability (trypan blue exclusion test) and for intracellular DNA, RNA and protein synthesis. None of the compounds tested had any effect on cell viability, or on RNA and protein synthesis apart perhaps from a slightly inhibitory action. While Trp-Fru remained ineffective also as far as intracellular DNA synthesis was concerned, both NO-Trp-Fru and NaNO2 had a major effect on DNA synthesis. With NaNO2, stimulation of DNA synthesis occurred at concentrations above 1 mM in the growth medium, but with NO-Trp-Fru synthesis increased at concentrations below 1 microM. The excess DNA synthesis (i.e. synthesis above control activity) observed with NO-Trp-Fru and also with NaNO2 was due to DNA repair. This was verified by keeping the cells under conditions that prevented normal semi-conservative replication but permitted DNA repair ('unscheduled DNA synthesis'). Two major routes are suggested by which NO-Trp-Fru could damage DNA.