The mechanisms by which DNA-incorporated radionuclides impart lethal damage to mammalian cells were investigated by examining the capacity of cysteamine (MEA) to protect against lethal damage to V79 cells caused by unbound tritium (3H2O), DNA-incorporated 131/125I-iododeoxyuridine (IdU) and the alpha-particle emitter 210Po-citrate. Radiolabeled cells were maintained at 10.5 degrees C for 72 h in the absence or presence of MEA (0.65-2.6 mM) and the surviving fraction was determined. Protection against lethal damage caused by 3H2O, 131IdU or 125IdU and 210Po-citrate depended on the concentration of MEA with maximum protection at 1.3-1.9 mM. The dose modification factors obtained at 1.3 mM for the radiochemicals were 2.5 +/- 0.3, 1.8 +/- 0.2, 1.7 +/- 0.1 and 1.4 +/- 0.1, respectively. MEA provides more protection against indirect than direct effects of ionizing radiation, and indirect effects play a role in the radiotoxicity of Auger electron emitters incorporated into the DNA of mammalian cells.