Toxicity of nanomaterials has been assessed by a number of ways, but nano-toxicity standards for biosafety or environment safety have not been established worldwide. It is likely that the final "standard approaches" shall include several components such as cytotoxicity, animal organ injury and body clearance of nanoparticles, while perturbed DNA replication fidelity resulted from nanomaterials is a particular point worthy of investigation for long-term toxicity assessment. This study reported a useful method to calculate the relative capacities of different nanoparticles to introduce DNA replication errors in the rpsL gene-based assays both in vitro (polymerase chain reaction, PCR) and in vivo. The method also offers a platform to develop various technologies in the context of DNA-nanoparticle interactions.