TESTING OF KNOWN CARCINOGENS AND NONCARCINOGENS FOR THEIR ABILITY TO INDUCE UNSCHEDULED DNA-SYNTHESIS IN HELA-CELLS

Abstract

The ability of 51 compounds, of known carcinogenic potential, to induce unscheduled DNA synthesis in HeLa human cervical cancer cells was 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 compounds from various classes of chemical carcinogens including nitrosamines, polycyclic aromatic hydrocarbons, aromatic amines and mycotoxins. Of the compounds assayed, all noncarcinogens failed to induce DNA repair. Of 38 compounds of demonstrated carcinogenicity, 34 were active. Safrole, N-propyl-N-nitrosourea, aflatoxin B2 and N-butyl-N-nitrosourea were inactive. Six compounds for which carcinogenicity data are incomplete were active, namely, 4-nitro-o-phenylenediamine, 2-nitro-p-phenylenediamine, formaldehyde, 2,2''-dichlorobenzidine, 3,3'',5,5''-tetrafluorobenzidine and 3,3'',5,5''-tetrachlorobenzidine. Three carcinogens that are weakly active or inactive in bacterial mutagenicity assays, i.e., urethan, N-dimethyl-p-aminoazobenzene and diethylstilbestrol were active in this assay. The bacterial mutagens sodium azide and 9-aminoacridine were inactive. The use of this assay in a tier scheme for the short-term testing of potential chemical carcinogens is discussed.