Testing of Known Carcinogens and Noncarcinogens for Their Ability to Induce Unscheduled DMA Synthesis in HeLa Cells1

The ability of 51 compounds, of known carcinogenic potential, to induce "unscheduled DMA synthesis" in HeLa cells has been tested in the presence or absence of a rat liver mixed-function oxidase preparation. Chemicals tested included those giving erroneous results in bacterial mutagenicity assays as well as representative com pounds from various classes of chemical carcinogens including nitrosamines, polycyclic aromatic hydrocar bons, aromatic amines, and mycotoxins. Of the com pounds assayed, all noncarcinogens failed to induce DNA repair; of 38 compounds of demonstrated carcinogenicity, 34 were active; safrole, N-propyl-N-nitrosourea, aflatoxin B..,and N-butyl-W-nitrosourea were, however, inactive. Six compounds for which carcinogenicity data are incomplete were active, namely, 4-nitro-o-phenylenediamine, 2-nitrop-phenylenediamine, formaldehyde, 2,2 -dichlorobenzidine, 3,3 ,5,5-tetrafluorobenzidine, and 3,3 ,5,5'-tetrachlorobenzidine. Three carcinogens that are weakly ac tive or inactive in bacterial mutagenicity assays, i.e., urethan, N-dimethyl-p-aminoazobenzene, and diethylstilbestrol were active in our assay. The bacterial mutagens sodium azide and 9-aminoacridine were both inactive. The use of this assay in a tier scheme for the short-term testing of potential chemical carcinogens is discussed.