Exposing HeLa S3 cells at 37 degrees C to varied concentrations of, respectively, Fru-Trp (0.1 microM - 1 mM), NO-Fru-Trp (0.1 microM - 1 mM), and NaNO2 (0.6 microM - 6 mM) for varied periods of time (1 - 36 hr) does neither affect their viability (trypan blue dye exclusion test) nor capability to synthesize RNA or protein but is of considerable influence on DNA synthesis in the case of NO-Fru-Trp and NaNO2, but not in the case of Fru-Trp which continues to be ineffective. None of the three compounds tested is of significant influence on cell number. Both NO-Fru-Trp and NaNO2 stimulate DNA synthesis: a maximum of activity [( 3H] thymidine incorporation) exists at the 24 hr time point of incubation, with NO-Fru-Trp, for instance, generating a 2.5-fold increase (over control) at 1 mM concentration in the medium while NaNO2, at comparable concentration, increases DNA synthesis by a factor of 1.6 over control. The increase in DNA synthesis is not due to stimulatory influences on (semi-conservative) DNA replication but represents DNA repair. This was verified by keeping the cells under conditions that prevent normal (semi-conservative) replication but permit repair ("unscheduled DNA synthesis"). Two major routes are suggested by which NO-Fru-Trp could impart DNA damage and, thus, assume mutagenic properties.